tbuckley/cabot-search huggingface dataset:
P4-17-03: Incidence Rate of Asymptomatic Brain Metastases in Patients with HER2+ Metastatic Breast Cancer Screened for EGF111438/CEREBEL Study.
Authors: X Pivot, J Hackmann, A Manikhas, Y Moore, R Parikh, D Kothari, A Joshi, G Aktan, R Coleman
Journal: Cancer Research (2011)

Abstract BACKGROUND Brain metastases constitute a major clinical concern occurring in 28–43% of women treated for HER2+ metastatic breast cancer (MBC). The initial diagnosis of Central Nervous System (CNS) lesion is commonly based upon development of neurological symptoms. Data to address incidence of CNS lesions in asymptomatic patients are rare and not generally reported. EGF111438/CEREBEL study requires systematic screening for brain metastases by brain MRI and the ineligible patients due to detection of asymptomatic brain metastases are reported here. METHODS The patients screened for CEREBEL have consented to a multi-centre, open-label Phase III study in subjects with HER2+ metastatic breast cancer who received prior treatment with anthracyclines or taxanes and trastuzumab in the adjuvant or metastatic setting. Eligible subjects must not have any history of CNS metastases (including leptomeningeal involvement) or have evidence of benign or malignant brain tumours and/or clinical evidence of spinal cord metastases at baseline. In order to confirm this, subjects must have negative brain MRI at baseline as confirmed by independent review (IR). All MRI scans of the brain had to be acquired with gadolinium contrast agent (T1 only) and 3mm slice thickness without gaps. The primary endpoint of CEREBEL is the incidence of CNS lesions as first site of relapse. A total of 650 subjects (325 per group) are expected to be randomized between capecitabine + trastuzumab versus capecitabine + lapatinib. RESULTS The study is currently recruiting with 322 patients enrolled as of 15.06.2011. At this date, the total number of patients screened were 492 and 170 of these patients were screen failures. There are 15 patients in screening. The percentage of screen failures due to asymptomatic brain metastases assessed by investigators was 13.5% (23/170). The overall incidence of clinically asymptomatic brain metastases assessed by investigators for this study is 4.7% (23/492). CONCLUSIONS Around 5% of all screened patients (14% of screen failures) in this study who were clinically thought to be free of brain lesions actually had brain metastases verified by brain MRI. We therefore conclude that screening for occult brain metastases by MRI is important for trials with defined CNS endpoints. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-17-03.
Long‐term persistence of host cells detected by X‐chromosome gene‐based assay in patients undergoing gender‐mismatched hematopoietic stem cell transplantation
Authors: Masamitsu Karasawa, Arito Yamane, Takeki Mitsui, Hiroyuki Irisawa, Tohru Sakura, Takafumi Matsushima, Norifumi Tsukamoto, Yoshihisa Nojima, Shuichi Miyawaki
Journal: American Journal of Hematology (2005)

Using our recently developed human androgen receptor (HUMARA) gene-based chimerism assay, long-term chimerism was investigated in female patients who underwent hematopoietic stem cell transplantation (HCT) with cells from male donors. After restriction digestion of samples, we detected a small number of female-derived cells within a large population of male-derived cells, with a sensitivity from 0.1% to 0.05%. Chimerism was examined in four patients with myeloid malignancies: two patients with acute myeloid leukemia (AML) from myelodysplastic syndrome (MDS), and one patient each with AML M3 and AML M4. All patients underwent myeloablative conditioning regimens and exhibited good clinical results during a median follow-up period of 6.6 years (range, 3.4-7.5 years). Female-derived cells were detected throughout the entire follow-up period in all bone marrow samples, but they became undetectable in the peripheral blood samples of 3 patients. Moreover, the HUMARA band pattern suggests that these residual host cells were normal cells. This study confirms the usefulness of the HUMARA gene-based assay, which showed that patients undergoing HCT frequently show mixed chimerism (MC) for a long period, especially in bone marrow, although the possibility of contamination by host stromal cells cannot be excluded.
THE INCIDENCE OF PELLAGRA IN OHIO HOSPITALS
Authors: WILLIAM BENNETT BEAN
Journal: JAMA (1942)

In the extensive medical literature there is no study which gives any comprehensive appraisal of the general incidence of pellagra. Such reports as are available come from public health reports, mortality statistics and figures for hospitalizations in areas where the condition has long been recognized as a menace to health. Furthermore, there is no indication of the prevalence of pellagra in regions of this country where it has not been studied intensively. As a consequence, there seems to be a widespread impression that this type of deficiency syndrome is very rare in the Northern states and exists only as a provincial problem peculiar to the endemic areas of the South. Indeed, case reports indicate that it is considered an exotic disease except in subtropical climates. For a number of years we have been engaged in the intensive study of pellagra in both sections of the country and have collected data
Soluble interleukin-2 receptor in Crohn's disease: relation of serum concentrations to disease activity.
Authors: J E Crabtree, L D Juby, R V Heatley, A J Lobo, D W Bullimore, A T Axon
Journal: Gut (1990)

Serum concentrations of soluble interleukin-2 receptor (sIL-2R) were measured as a marker of immune activation in a group of 30 patients with Crohn9s disease. sIL-2R concentrations were determined by enzyme linked immunosorbent assay during periods of active and inactive disease and correlated with standard parameters of disease activity. Serum concentrations of sIL-2R were significantly raised in patients with active Crohn9s disease compared with patients with inactive disease (p less than 0.001) and control subjects. There was a significant correlation between serum sIL-2R concentrations and disease activity as assessed by the Harvey-Bradshaw index (r = 0.42, p less than 0.01), platelet numbers (r = 0.49, p less than 0.01), and orosomucoid (r = 0.47, p less than 0.01), alpha 1 antitrypsin (r = 0.44, p less than 0.01), and C reactive protein concentrations (r = 0.48, p less than 0.001) but not with the erythrocyte sedimentation rate. Measurement of serum sIL-2R concentration is a simple and useful laboratory means of assessing disease activity. Raised concentrations in patients with active Crohn9s disease is further evidence for in vivo immune activation occurring in this disease.
108. Study of an AAV-8 Capsid Mutant with Direct Heparin Binding Capability but Reduced Efficiency in Liver-Targeted Transduction
Authors: Xuan Shen, Hui Xu, Theresa Storm, Mark A. Kay
Journal: Molecular Therapy (2006)

Top of pageAbstract
AAV vectors pseudotyped with the AAV-8 capsids have become a popular alternative to the more extensively studied AAV-2 vectors due to their more robust transduction of liver and other targets in vivo. Importantly, liver transduction with AAV-2 is significantly higher when the vector is administered into the liver vasculature compared to a peripheral venous infusion (e.g. tail vein). In contrast, there are no differences in liver transduction efficiencies when AAV- 8 vectors were administered via these two different routes. Despite the high degree of sequence homologies (|[sim]|83%), the two capsids differ in their cell surface binding properties. Because wild type AAV-8 cannot directly bind to heparin, whose analog, heparan sulfate proteoglycan (HSPG), is a primary cell surface receptor for AAV-2, we hypothesized that the heparin binding motif may play a role in the observed differences in the hepatic transduction parameters. Sequence alignment revealed that the AAV-8 cap gene lacks two basic amino acid residues found in AAV-2 (R585, R588) that are essential for heparin binding. By substituting the corresponding AAV-8 residues at these and neighboring positions with AAV-2 sequence, we generated a mutant AAV-8 (mAAV-8) capsid with direct heparin-binding affinity similar to that of AAV-2.

We made liver-specific human factor IX (hFIX)-expressing vectors in AAV-2, AAV-8 or the mAAV-8 capsids respectively, and compared their liver transduction efficiencies following intravenous administration into C57BL/6 mice. Depending on the route of injection, hFIX expression levels from the mAAV-8 vector were three and ten times lower than that of AAV-8 when administered via portal vein and tail vein, respectively. These differences in transduction with peripheral and liver vascular infusions were similar to what we observed with AAV-2, suggesting that the heparin binding motif may influence differing transduction efficiencies when administered by different vascular routes. To further establish this possibility, vector bio-distribution in various tissues was also checked by real-time PCR quantitation of viral genomes at different time points following vector administration. We found that the mAAV-8 capsid showed broader tropism and less targeting in the liver when administered via tail vein. Further experiments are being carried out to examine the intracellular trafficking pathways of vectors made with each of these capsids but our results suggest that vector biodistribution and perhaps intracellular transduction pathways are influenced by the presence of the heparin binding motif.
Unusual Involvement of Scalp and Bilateral Kidneys in an Aggressive Mediastinal Diffuse Large B Cell Lymphoma
Authors: Sandip Basu, S K. Ramani, S Lad
Journal: Clinical Nuclear Medicine (2009)

In the present communication, an unusual combination of scalp soft tissue and underlying brain involvement with intact skull bone coupled with bilateral renal involvement from a mediastinal diffuse large B cell lymphoma (DLBL) is presented. A 45-year-old man, a diagnosed case of mediastinal DLBL with bilateral lung involvement, was treated with conventional 6 cycles of chemotherapy and local external radiotherapy with initial good treatment response evidenced by considerable regression in mass size and regression in pulmonary lesions. Three months later, he returned with complaints of soft tissue swelling over the scalp; one of them in the high parietal bone and the other over the occipital region. A whole body FDG-PET at this time showed 2 moderate-sized foci in the scalp (with preservation of both tables of skull bone) and corresponding large foci in the brain parenchyma beneath, a superior mediastinal focus, a few foci in the apical and lower zone of left lung, extensive irregular uptake in the right pleura and the right lung parenchyma coupled with a loculated effusion in its lower zone and studded foci of hypermetabolism throughout the bilaterally enlarged kidneys. CT of the head confirmed the FDG-PET findings and histopathology of the biopsy from the scalp swelling was suggestive of DLBL. Ultrasound imaging of the abdomen showed lobulated bilaterally enlarged kidneys with multiple hypoechoic areas within them. The patient underwent palliative local external radiotherapy to the brain and systemic chemotherapy with poor clinical results with raised serum beta-2 microglobulin and serum LDH levels and deranged renal function. The patient died within a month after the FDG-PET study. The event of scalp and bilateral renal involvement from DLBL is rare in lymphoma literature and this report highlights that such unusual events can occur as part of widespread dissemination and underscores the importance of whole-body imaging with FDG-PET.
Risk of cancer in an occupationally exposed cohort with increased level of chromosomal aberrations.
Authors: Z Smerhovsky, K Landa, P Rössner, M Brabec, Z Zudova, N Hola, Z Pokorna, J Mareckova, D Hurychova
Journal: Environmental Health Perspectives (2001)

We used cytogenetic analysis to carry out a cohort study in which the major objective was to test the association between frequency of chromosomal aberrations and subsequent risk of cancer. In spite of the extensive use of the cytogenetic analysis of human peripheral blood lymphocytes in biomonitoring of exposure to various mutagens and carcinogens on an ecologic level, the long-term effects of an increased frequency of chromosomal aberrations in individuals are still uncertain. Few epidemiologic studies have addressed this issue, and a moderate risk of cancer in individuals with an elevated frequency of chromosomal aberrations has been observed. In the present study, we analyzed data on 8,962 cytogenetic tests and 3,973 subjects. We found a significant and strong association between the frequency of chromosomal aberrations and cancer incidence in a group of miners exposed to radon, where a 1% increase in frequency of chromosomal aberrations was followed by a 64% increase in risk of cancer (p < 0.000). In contrast, the collected data are inadequate for a critical evaluation of the association with exposure to other chemicals.
TRAUMATISM OF THE CHEST.Read in the Section of Surgery and Anatomy, at the Forty-second Annual Meeting of the American Medical Association, Washington, D. C., May 5, 1891.
Authors: J. McFADDON GASTON
Journal: JAMA (1891)

In the course of my investigations on thoracic surgery for the<i>Annual of the Universal Medical Sciences</i>, I have been strongly impressed with the lack of knowledge in regard to the injuries of the chest. While this subject has been considered somewhat carefully in my two contributions to that work, there are many practical details of great importance which are not touched upon, owing to the paucity of data afforded by the very limited reports in this branch of surgical experience. It is not my purpose now to enter into the minute distinctions of the lesions resulting from violence to the walls and contained viscera of the chest. I ask for the attention of surgeons to the great advantage of methodic treatment of traumatism of the chest. All those inflammatory processes of a latent or idiopathic nature, which lead to serous effusions primarily or to suppuration secondarily, within the
CLINICAL INDICATIONS FOR INDUCING GASTRIC HYPOMOTILITY
Authors: FRANK E. HAMILTON
Journal: JAMA (1941)

The motor activity of the human stomach is of demonstrable clinical significance. This is particularly true in those patients with lesions involving viscera innervated by the extended vagi. Moreover, it appears that the clinical management of certain patients may often be aided by an increased knowledge of stomach activity.  Members of the Surgical Research Department of the Ohio State University have during the past few years investigated the motor activity of the stomach of a large number of patients under a variety of clinical conditions. Using the balloon and kymograph method, we have found that the normal motility is affected not only by disturbances in gastric physiology but also by certain pathologic lesions occurring elsewhere along the gastrointestinal tract.  More recently we have studied alterations in the motor activity which may be observed in patients presenting certain common abdominal complications. Many patients complained of pain or discomfort simultaneously with obvious
Long-term Follow-up Reveals Low Incidence of Colorectal Cancer, but Frequent Need for Resection, Among Australian Patients With Inflammatory Bowel Disease
Authors: Christian P. Selinger, Jane M. Andrews, Andrew Titman, Ian Norton, D. Brian Jones, Charles McDonald, Gavin Barr, Warwick Selby, Rupert W. Leong
Journal: Clinical Gastroenterology and Hepatology (2013)
Surgical Cure of Chronically Discharging Ear Previously Subjected to Mastoidectomy
Authors: Milo H. Fritz
Journal: JAMA (1960)

Reference is made to the procedures for treatment of the chronically discharging ear, treated unsuccessfully with mastoidectomy. According to the medical histories of 20 patients there was a return of symptoms possibly related to upper respiratory tract infection or the passage of water into the ear. The surgical procedure devised by J. H. T. Rambo and used satisfactorily by the author consists of the introduction of a large tongue of temporalis muscle into the combined middle ear and mastoid cavity following the radical operation. This, with skin flaps developed from the lining of the external canal, effects a primary closure. There has been the added value of improved blood supply.
Reproductive functions of the ageing male
Authors: B. Kuhnert
Journal: Human Reproduction Update (2004)

Delayed childbearing is a common phenomenon in industrialized countries. This review focuses on age-associated alterations of male fertility and genetic risks. Semen volume, sperm motility and sperm morphology decrease with age, whereas the data concerning sperm concentration are conflicting. The age-related changes of semen parameters reflect the histological modifications which are found to varying degrees in individual testes. Men aged >40 years contribute to reduced fertility and fecundity of a couple, especially when the female partner is also of advanced age. Because relatively few children are born to older fathers and genetic diseases are rare, there is little statistical power supporting an association of genetic diseases in the offspring with advancing paternal age. Nevertheless, autosomal dominant diseases and some diseases of complex aetiology, such as schizophrenia, are associated with advancing paternal age. The single point mutations in sperm which are responsible for achondroplasia and Apert's syndrome, two autosomal dominant diseases, increase with the man's age. In case of Apert's syndrome this increase is believed to be due to a pre-meiotic selection of mutant spermatogonia. Although structural chromosome anomalies and disomies of certain chromosomes increase in sperm with the man's age, paternal age is, with the exception of trisomy 21, not associated with numerical or de novo structural chromosomal aberrations in newborns. However, even if the genetic risk for progeny from older fathers is slightly increased, the risk to the individual is low.
REMARKS ON VAGINAL HYSTERECTOMY.
Authors: L. H. DUNNING
Journal: JAMA (1894)

Vaginal hysterectomy is an operation so frequently done with such a high degree of success by so many different surgeons that I would not attempt to remark upon it, had I not had an unusual experience in two recent cases. Having had my attention called to Pratt's modification of the operation, I procured copies of the<i>Medical Century</i>containing several articles by the author of the method, and others who had observed his work. The essential characteristics of his operation, so far as they differ from other methods, are as follows: The uterine cavity is tightly packed with antiseptic candle-wicking to distend the uterus and make distinct its outlines. The Simons' position is employed and the uterus brought into view in the usual manner and stout threads passed through the anterior and posterior lips of the cervix. The initial cut around the cervix is made nearer the os than usual.
Charles Gabriel Seligman
Authors: Leonard B. Glick
Journal: New England Journal of Medicine (1960)

EARLY in 1898, a small band of Cambridge scholars prepared for an unusual adventure: a research expedition to primitive New Guinea and adjoining islands. The group, assembled by Alfred C. Haddon, biologist turned ethnologist, boasted a variety of talents. Two of its members were W. H. R. Rivers, a medically trained physiologist and psychologist, and his pupil, C. S. Myers; they were to study the sensory perceptions of the natives and obtain information on primitive psychology. Anthropology was then in its infancy as a science; Rivers and Myers were to demonstrate for the first time that primitive people did not . . .
PSYCHIC AND EMOTIONAL FACTORS IN GENERAL DIAGNOSIS AND TREATMENT
Authors: ROLLIN T. WOODYATT
Journal: JAMA (1927)

A few months ago I saw a patient in an attack of acute abdominal pain so strongly suggesting an obstruction of the large bowel that a surgeon was called. This was at night. The pain had begun in the morning. By the time the surgeon arrived, the pain had subsided somewhat. It was therefore decided to wait before proceeding with any surgical measures. In the morning, when the patient was somewhat better, a fluoroscopy of the large bowel showed the barium filling the rectum and sigmoid to a point 14 inches above the sphincter, but it was impossible to make the barium pass any higher. Meanwhile, as the mass filled the bowel below this point, the patient complained bitterly of pain, which he said was of the same character and in the same part of the abdomen as that which he had had the day before. Several films were made,
Abstract 907: Subtypes, race and long-term survival in the Carolina Breast Cancer Study
Authors: Katie M. O'Brien, Robert C. Millikan, Stephen R. Cole
Journal: Cancer Research (2010)

Abstract Previous analyses from the Carolina Breast Cancer Study identified significant differences in breast cancer (BC) specific mortality across the four ‘intrinsic’ BC subtypes: luminal A, luminal B, basal-like, and human epidermal growth factor receptor 2 positive / estrogen receptor negative (HER2+/ER-). Here, we expand the assessment by including additional cases and longer follow-up time, and present analyses stratified by race and menopausal status. We used immunohistochemical markers to subtype 1149 invasive BC cases (518 Black, 631 Non-black) in this population-based epidemiologic study of women diagnosed with BC in North Carolina between 1993 and 2001. Vital status was determined through 2006 using the National Death Index, with median follow-up of 9.1 years. Hazard ratios (HRs) were estimated using Cox proportional hazards models for BC-specific mortality. Compared to Luminal A, women with HER2+/ER- BC had the highest mortality (HR=2.3, 95% CI: 1.5, 3.6, adjusting for age at diagnosis, race, and year of diagnosis), followed by basal-like BC (HR=1.7, 95% CI: 1.2, 2.4). Differences in mortality by subtype remained, albeit attenuated, after further adjustment for stage at diagnosis. Race-stratified HRs were similar for HER2+/ER- BC (HR=2.4, 95% CI: 1.2, 4.7 and HR=2.3, 95% CI: 1.3, 4.0 for non-Blacks and Blacks, respectively), but appeared to differ for basal-like BC (HR=2.0, 95% CI: 1.2, 3.4 for non-Blacks and HR=1.5, 95% CI: 1.0, 2.4 for Blacks). For basal-like BC, mortality was slightly higher among premenopausal, non-Black women (HR=1.8, 95% CI: 1.0, 3.4) compared to premenopausal Black women (HR=1.3, 95% CI: 0.8, 2.3). HRs for basal-like versus Luminal A BC were highest among postmenopausal women (HR=3.9, 95% CI: 1.5, 10.0 for non-Blacks; HR=1.9, 95% CI: 0.9, 3.8 for Blacks). Stage, tumor size and lymph node status were associated with mortality in all subtypes. We also used flexible models to permit departures from the proportional hazards assumption and therefore allow HRs for BC to vary over time since diagnosis. In summary, these results confirmed previous analyses that during a time interval prior to the introduction of Herceptin®, HER2+/ER- cases exhibited the highest mortality of the four subtypes. Possible racial differences in mortality were observed according to BC subtype. Additional analyses are needed in populations with known treatment profiles to more fully understand the role of intrinsic subtypes and race in BC survival. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 907.
Ocular and Systemic Autoimmunity after Successful Tumor-Infiltrating Lymphocyte Immunotherapy for Recurrent, Metastatic Melanoma
Authors: Steven Yeh, Neel K. Karne, Sid P. Kerkar, Charles K. Heller, Douglas C. Palmer, Laura A. Johnson, Zhuqing Li, Rachel J. Bishop, Wai T. Wong, Richard M. Sherry, James C. Yang, Mark E. Dudley, Nicholas P. Restifo, Steven A. Rosenberg, Robert B. Nussenblatt
Journal: Ophthalmology (2009)