tbuckley/cabot-search huggingface dataset:
Study of clinical, biochemical and immunological factors determining stability of disease in patients with generalized vitiligo undergoing melanocyte transplantation
Authors: A. Rao, S. Gupta, A.K. Dinda, A. Sharma, V.K. Sharma, G. Kumar, D.K. Mitra, C.K. Prashant, G. Singh
Journal: British Journal of Dermatology (2012)

Stability is considered the most important parameter before performing any melanocyte transplantation procedure in vitiligo; however, current criteria rely on the history given by the patients.This study was undertaken to determine the clinical, biochemical and immunological factors determining stability of disease in patients with generalized vitiligo to facilitate better patient selection for melanocyte transplantation and to understand immunological mechanisms for disease activity.Thirty-three patients with generalized vitiligo with < 10% body surface area involved were allocated to three clinical stability groups: Group 1 (stability > 3 months but < 1 year), Group 2 (≥ 1 year but < 2 years) and Group 3 (≥ 2 years). Melanocyte transplantation was done using suction blister epidermal grafting (SBEG) on a single patch. Blood was drawn for catalase estimation from all patients and from 10 healthy control subjects. A 3-mm punch biopsy was taken on the day of transplantation from the margin of the macule in the first five patients in each group for the immunohistochemistry of CD4, CD8, CD45RO, CD45RA and FoxP3. Those with ≥ 75% repigmentation at 6 months were labelled as responders.The success rate was 0% in Group 1, 37·5% in Group 2 and 77·8% in Group 3. The difference in the success rate between the groups was statistically significant (P = 0·005). The median period of stability was significantly higher in the responders compared with that in the nonresponders (P = 0·001). Catalase levels were not significantly different between patients in the three groups of cases and in controls, or between responders and nonresponders. Lesional CD8 cells were significantly higher in Group 1 compared with Group 3. The percentages of CD8 and CD45RO cells were significantly higher in the nonresponders compared with the responders.Along with clinical stability, the proportion of CD8 and CD45RO cells in skin biopsies might help to determine the stability of the disease and thereby predict the success of transplantation.
Editorial: Is It Time for Epigenetics in Osteoarthritis?
Authors: Francisco J. Blanco, Ignacio Rego‐Pérez
Journal: Arthritis & Rheumatology (2014)

DNA methylation is an epigenetic mechanism of reversible gene regulation which typically results in gene silencing upon hypermethylation in high CpG density regions of promoters (termed CpG islands), and increased gene expression when methylation occurs in gene bodies.Prior information on OA-associated changes in DNA methylation are limited to important single gene analyses and two studies on genome wide changes in cartilage and subchondral bone.Rushton et al present elegant work characterizing the genome-wide DNA methylation profile in articular cartilage from normal and OA-affected hip and OA-affected human knee joints.Resultsshow that normal and OA hip cartilage have a unique methylation profiles, with 5322 differentially methylated loci (DMLs) identified between both groups.They also show that OA hip and knee samples can be separated into two clusters based on their methylation profile.In total 15239 DMLs were identified between the two hip OA clusters, with an enrichment of genes involved in inflammation and immunity.The identification and isolation of subgroups with different methylation profiles may also be critical for the development of effective disease prevention and treatment, and to characterize the different OA phenotypes such as inflammatory, aging and metabolicrelated.
Therapy of refractory or recurrent childhood acute myeloid leukemia using amsacrine and etoposide with or without azacitidine: a Pediatric Oncology Group randomized phase II study.
Authors: C P Steuber, J Krischer, T Holbrook, B Camitta, V Land, C Sexauer, D Mahoney, H Weinstein
Journal: Journal of Clinical Oncology (1996)

PURPOSE A randomized study compared the combination of amsacrine (100 mg/m2/d on days 1 to 5) and etoposide (200 mg/m2/d on days 1 to 3) with the same two agents plus azacitidine (250 mg/m2/d on days 4 to 50) for the therapy of induction-resistant or relapse childhood acute myeloid leukemia (AML). PATIENTS AND METHODS One hundred sixty-seven assessable children with AML who either had failed to respond to primary induction therapy (group 1, n = 41) or had relapsed (group 2, n = 126) were randomized. RESULTS Overall, there were 56 complete responses (34%; SE 4%). Among primary refractory patients (group 1), the complete response rate was higher with the three-drug regimen (18% vs 53%, P = .03). In the relapsed patients (group 2), there was no difference in complete response rates related to treatment (31% vs 35%, P = .3). There were 17 early deaths. The major toxicities for both regimens were myelosuppression and infection. CONCLUSION The overall complete response rate of 34% in this patient population is indicative of effective antileukemic activity. For patients with relapsed leukemia, the addition of azacitidine to etoposide and amsacrine did not improve response. The suggested advantage of the three-drug regimen for induction failures warrants further investigation.
TNFerade combined with chemoradiation in resectable esophageal cancer
Authors: N. Hanna, N. Senzer, T. Reid, T. Chung, K. J. Chang, P. Kessler, A. Mauer, M. Posner, J. Nemuniatis, S. Swisher
Journal: Journal of Clinical Oncology (2004)

3197 Background: TNFerade is a second-generation replication deficient adenovector, carrying the transgene encoding for human TNFα, regulated by the radiation-inducible promoter Egr-1. A dose-escalating study was initiated to demonstrate feasibility, safety and tolerability of TNFerade combined with chemoradiotherapy in patients receiving preoperative chemoradiation for resectable esophageal cancer. An additional aim of this study was to select the dose of TNFerade for phase II evaluations. Methods: TNFerade was administered weekly x 5 concurrently with radiotherapy (45 Gy) and 5-FU (1000 mg/m2/day for 96 hrs on Day 1 and Day 29) plus cisplatin (75 mg/ m2 on Day 1 and Day 29). TNFerade was administered via endoscopic intratumoral injection, using ultrasound guided injection or endoscopic injection according to study site preference. The study endpoints were safety, feasibility, and response rate, assessed by histopathologic evaluation of resection specimens. Results: 11 patients have been treated in the 4x108 pu and 4x109 pu cohorts, and enrollment is ongoing. Enrolled patients have all had T3 staging; 9/11 were adenocarcinoma; 2/11 squamous carcinoma. Repeated administration of TNFerade via endoscopy during chemoradiotherapy was feasible and well tolerated with the maximally tolerated dose not yet reached. Adverse events (AE) have been analyzed for the first dosing cohort (N=7). AEs thought to be related to TNFerade have all been NCI grade 1–2 and include fatigue (43%), pain (29%) and dysphagia, nausea, esophageal spasm, esophagitis, and rigors (14 %). Serum TNF-a levels were less than 11 pg/ml (upper limit of normal 8.3 pg/ml). Viral cultures of urine and blood were negative. Neutralizing antibodies to adenovirus were detected at baseline in 3/7 patients (4x108 pu cohort) and were elevated at end of treatment in all but one patient. A complete pathologic response was reported in 1/6 resected at the lowest dose. Conclusion: Early data suggest repeated endoscopic injections of TNFerade in combination with chemoradiation is feasible. Data for the first three dosing cohorts will be presented. This study will help provide the basis for a scheduled phase II study in esophageal cancer. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GenVec GenVec GenVec GenVec Inc.
Diet in the Epidemiology of Cancer of the Colon and Rectum&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Saxon Graham, Hari Dayal, Mya Swanson, Arnold Mittelman, Gregg Wilkinson
Journal: JNCI Journal of the National Cancer Institute (1978)

We examined the diets as reported in interviews of 256 white male patients with cancer of the colon and of 330 white male patients with cancer of the rectum. Controls were 783 patients with nonneoplastic, nondigestive system diseases distributed by age similarly to the colon cancer patients and 628 patients with nonneoplastic, nondigestive diseases distributed by age like those with cancer of the rectum. We found no increase in risk for cancer of the colon or rectum regardless of the amounts of beef or other meats ingested. However, we found an increase in risk of colon cancer with decreases in the frequency with which vegetables were eaten. A study of 214 females with cancer of the colon and 182 females with cancer of the rectum yielded similar results. The decrease in risk we found associated with frequent ingestion of vegetables, and especially cabbage, Brussels sprouts, and broccoli, is consistent with the decreased numbers of tumors observed in animals challenged with carcinogens and fed compounds found in these same vegetables.
Adjuvant chemotherapy with doxorubicin plus cyclophosphamide, methotrexate, and fluorouracil in the treatment of resectable breast cancer with more than three positive axillary nodes.
Authors: R Buzzoni, G Bonadonna, P Valagussa, M Zambetti
Journal: Journal of Clinical Oncology (1991)

To improve current adjuvant results in high-risk breast cancer, in February 1982 we activated a prospective randomized trial using both intravenous cyclophosphamide, methotrexate, and fluorouracil (CMF) and Adriamycin (doxorubicin; Farmitalia-Carlo Erba, Milan, Italy) involving patients with resectable mammary carcinoma and more than three positive axillary lymph nodes. The objective of the study was to assess the effectiveness of four courses of Adriamycin followed by eight courses of CMF versus two courses of CMF alternated with one course of Adriamycin for a total of 12 courses. All drug courses were recycled every 3 weeks. Rather than temporarily reducing doses in the event of myelosuppression on the planned day of treatment, drug administration was delayed for 1 to 2 weeks. At a median follow-up of 59 months, treatment outcome was significantly superior for patients who received Adriamycin followed by CMF (Adriamycin----CMF) than for those given alternating regimens (CMF/Adriamycin). The 5-year relapse-free survival was superior post-Adriamycin----CMF (61%) compared with post-CMF/Adriamycin administration (38%; P = .001). The corresponding figures for the 5-year total survival were 78% and 62%, respectively (P = .005). The benefit of Adriamycin----CMF was observed in all patient subsets. Treatment was fairly well tolerated, and we documented only one case of fatal congestive heart failure in a patient who received postoperative irradiation to the left breast in addition to Adriamycin. Present findings indicate that in women with extensive nodal involvement, Adriamycin----CMF yielded superior results compared with CMF/Adriamycin.
Skin lesion in a critically ill man
Authors: Ming-Hua Zheng, Ke-Qing Shi, Yong-Ping Chen
Journal: BMJ (2015)

A 45 year old man was referred to the emergency department with a seven day history of high fever and chills. His condition suddenly deteriorated and he presented with dark yellow urine of decreased volume, tachypnoea, and drowsiness. His medical history included hypertension, type 2 diabetes, and heavy consumption of alcohol (>6.8 units, or >50 g alcohol/day for 12 years). He had travelled to a mountainous region in Fujian province of China 12 days earlier.

On admission to intensive care, he was found to have a round ulcer near the navel, 3 mm in diameter, with marginal swelling and peripheral blushing (fig 1⇓). The rest of his physical examination, including the cranial nerve, was normal. Table 1 shows the results of his blood tests⇓. No obvious abnormality was visible on routine computed tomography of the brain and lung; however, hepatomegaly and a slight splenomegaly were seen on a computed tomogram of his abdomen.

View this table:

Table 1 
The patient’s laboratory test results in the intensive care unit





Fig 1 Skin lesion in the abdomen





### 1. What is the differential diagnosis?

#### Short answer

Tsutsugamushi disease (severe type), typhoid fever, relapsing fever, and epidemic haemorrhagic fever.

#### Discussion

The final diagnosis was tsutsugamushi disease (severe type), a rickettsial disease, which is an acute lethal infectious disease caused by Orientia tsutsugamushi . The micro-organism is introduced through the skin by the bite of a larval stage trombiculid mite. It occurs in people who visit mite infected habitats such as brush and grass. It is an emerging and re-emerging condition in many Asian countries, including China, Japan, Korea, and other countries in east and South …
Evaluating the usefulness of spa typing, in comparison with pulsed-field gel electrophoresis, for epidemiological typing of methicillin-resistant Staphylococcus aureus in a low-prevalence region in Sweden 2000–2004
Authors: A.C. Petersson, B. Olsson-Liljequist, H. Miörner, S. Hæggman
Journal: Clinical Microbiology and Infection (2009)
Our experience of procalcitonin assay in identifying bacterial COPD exacerbations
Authors: Christopher Gough, Parthipan Pillai, Rohinton Mulla
Journal: European Respiratory Journal (2011)

Background: Procalcitonin (PCT) is a pre-hormone which is raised in bacterial infection.  Aim of study: To evaluate the benefit of measuring PCT level in recognising bacterial from non bacterial COPD exacerbations.  Method: We prospectively evaluated 24 COPD patients who were admitted with an exacerbation. They had PCT, C-reactive protein (CRP), white blood cell (WBC) measurements and a chest radiograph (CXR). Use of antibiotics were recorded.  Results: 6 patients had CXR findings of consolidation and 5 of them had high PCT indicating bacterial infection. 1 patient had a moderately elevated PCT which could be due to early sampling.  In 18 patients who had normal CXR findings, 3 had positive PCT and of these, 1 had high CRP and WBC indicating true bacterial infection. 1 had high CRP with normal WBC which could be due to atypical bacterial infection. 1 had normal CRP with high WBC which could be due to spuriously low CRP result.  In 15 patients who had negative PCT, 7 had normal CRP and WBC indicating no bacterial infection. 2 of them had normal CRP but slightly raised WBC and we feel the raised WBC were due to preceding steroid treatment. 3 of them had raised CRP and normal WBC and 3 had both raised CRP and WBC. These may be due to bacterial infection, and the negative PCT represented early sampling. All patients had antibiotics on admission.  Conclusion: Many patients with COPD exacerbation are treated with antibiotics without bacterial infection. High PCT level indicates bacterial infection in these patients. The converse is also true but this should be used in conjunction with CRP and WBC levels. When normal PCT level is associated with either raised CRP or WBC, a second late PCT level should be measured.
Preferential Iron Trafficking Characterizes Glioblastoma Stem-like Cells
Authors: David L. Schonberg, Tyler E. Miller, Qiulian Wu, William A. Flavahan, Nupur K. Das, James S. Hale, Christopher G. Hubert, Stephen C. Mack, Awad M. Jarrar, Robert T. Karl, Ann Mari Rosager, Anne M. Nixon, Paul J. Tesar, Petra Hamerlik, Bjarne W. Kristensen, Craig Horbinski, James R. Connor, Paul L. Fox, Justin D. Lathia, Jeremy N. Rich
Journal: Cancer Cell (2015)
ECME: Epidemiologic study of the characteristics of women with COPD in Spain
Authors: Sagrario Mayoralas, Salvador Diaz Lobato, Esther Anton, Xavier Ribera, Irune Unzueta
Journal: European Respiratory Journal (2011)

Background:  Chronic obstructive pulmonary disease (COPD) clinical trial populations are often predominantly male (∼75%), thus the female population is not so well characterized.   Aims and objectives:  Determine a clinical and sociodemographic profile of women with COPD in Spain.   Methods:  Multicenter, cross-sectional, observational epidemiological study. 379 pulmonologists from health centers in Spain recruited female patients aged ≥40 yrs, smoking history ≥10 pk-yrs, current COPD diagnosis and receiving treatment/follow-up during pulmonologist visits. Clinical and sociodemographic data were collected during study visit. Descriptive statistics were performed.   Results:  1732 women evaluated, of which: 80.8% pulmonologist diagnosis; 46.6% primary, 30.8% secondary education; 60.1% current-, 39.9% ex-smokers; 25.5% and 43.1% with history of depression or anxiety, respectively; 78.3%, 65.3%, 63.1% receiving long-acting anticholinergic, long-acting β 2 -agonist/corticoid, short-acting β 2 -agonists. Mean±SD values: age, 61.6±10.0 yrs; body mass index, 26.7±5.1 kg/m 2 ; time since, and age at, diagnosis, 7.5±6.4 yrs and 54.1±9.8 yrs; pre- and post-bronchodilator FEV 1 /FVC, 57.5±12.3% and 57.8±12.2%; O 2  saturation, 93.8±3.3%; PYI, 35.7±19.9; SF-12 PCS and MCS scores, 37.6±10.5 and 45.7±12.0; LCADL total, personal care, and household, physical, leisure activities, 27.2±10.9, 6.5±2.9, 11.8±5.9, 4.5±1.6, 4.4±1.8. Median no. exacerbations in prior year, 1.0 (P25/P75: 0.0/2.0)   Conclusions:  Most women in this cross-sectional study were at an age that they could be actively working. The average FEV 1  and exacerbation history suggest an impact of the disease on these patients9 daily lives.  Funded by Boehringer Ingelheim/Pfizer.
Geographic Patterns for Pleural Mesothelioma Deaths in the United States, 1968–81&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: P E Enterline, V L Henderson
Journal: JNCI Journal of the National Cancer Institute (1987)

Deaths and death rates for mesothelioma of the pleura are presented by age, sex, and geographic area for the United States for the years 1968-81. Death rates increased with age and in every age group were roughly three times higher for males than for females. Over the period 1968-81, death rates increased for males aged 65 years or more, whereas death rates in other age-sex groupings remained fairly constant or declined slightly. It is known that asbestos is highly related to mesothelioma, and the increase in death rates among older males could be due to asbestos. Conversely, the fact that death rates in younger males and in females have not been increasing suggests some kind of background level not strongly related to the use of asbestos. When the geographic distribution of death rates was examined by state, there was considerable geographic variation with some clustering. High death rates for males appeared for the Northeastern States and along the Pacific Coast, and for Illinois, Florida, Wyoming, and Colorado. Females shared this geographic pattern to some extent. When death rates were examined by county, a relationship was seen between pleural mesothelioma deaths among males and the presence of asbestos products plants and shipbuilding facilities. Excessive death rates in some counties and states did not appear to be related to asbestos exposure. Although the similarity in geographic patterns of mortality for males and females suggests a common etiology, the trends in mortality suggest different etiologies. There may be important causes of pleural mesothelioma yet to be identified.
Goserelin, a depot gonadotrophin-releasing hormone agonist in the treatment of premenopausal patients with metastatic breast cancer. German Zoladex Trial Group.
Authors: M Kaufmann, W Jonat, U Kleeberg, W Eiermann, F Jänicke, J Hilfrich, R Kreienberg, M Albrecht, H K Weitzel, H Schmid
Journal: Journal of Clinical Oncology (1989)

One hundred thirty-four pre- and perimenopausal patients presenting with metastatic breast cancer (median age, 42 years; range, 25 to 55) were treated with goserelin (Zoladex [ICI 118 630]; ICI Pharma, Plankstadt, Germany) a long-acting gonadotrophin-releasing hormone (GnRH)-analogue depot formulation, injected subcutaneously every 4 weeks, as a first-line therapy. One hundred eighteen patients were evaluable for response. Serum concentrations of estradiol, luteinizing hormones (LH), and follicle-stimulating hormones were significantly suppressed by Zoladex. Mean serum estradiol values fell into the range of castrated or postmenopausal women within 2 to 3 weeks of therapy. This suppression was maintained for the duration of therapy. Overall objective response was: 12 (10.2%) complete remission; 41 (34.7%) partial remission; 33 (28.0%) no change; and 32 (27.1%) progression. In responders, the median time to response was 4 months (range, 2 to 11 months), median duration of response was 8 + months (range 2 to 24 months), and median time to progression was 11 + months (range, 5 to 30 months). Objective responses were seen for different sites of metastases: loco-regional (62.5%), bone (46.7%), visceral (45.0%), and multiple (35.1%). Tumor remission was more common in patients in which the primary tumor was estrogen receptor (ER)-positive (49.3%) or ER-unknown (44.0%), but appreciable response rates were also observed in ER-poor patients (33.3%). Zoladex depot was well tolerated both locally and systemically. It produced effective castration and the objective response rates and duration of remission are at least comparable to those seen following oophorectomy; however, the side effects are less. The use of depot Zoladex avoids the psychological trauma and operative morbidity of the irreversible operative castration.
Characterization of Tumorigenic and Metastatic Properties of Murine Sarcoma Virus-Transformed Nonproducer Balb/3T3 Cell Lines&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: Ganesa Yogeeswaran, Barry S. Stein, Henry Sebastian
Journal: JNCI Journal of the National Cancer Institute (1980)

The tumorigenic and metastatic properties of independently derived tissue culture lines of murine sarcoma virus (MuSV)-transformed nonproducer Balb/3T3 cells were evaluated for five characteristics: 1) [125I]-5-iodo-2′ -deoxyuridine tumor cell take, 2) tumor growth, 3) spontaneous regression, 4) metastasis from progressive tumor growth, and 5) metastatic assay following excision of the tumor at constant size. The studies revealed that two independent transformed clones of Moloney (M)-MuSV-transformed cells (MuSV85 CI 3 and MuSV85 CI 3/CI 7B) and one clone of Kirsten(Ki)-MuSV-transformed cells (KB521) were weakly tumorigenic. These transformants showed a low percentage of subcutaneous tumor cell takes, a slow tumor growth rate, and a moderate degree of tumor regression. The frequency of spontaneous pulmonary metastasis of the M-MuSV-transformed clone and its subclone was 0–5%, judged either at the time of death due to the primary tumor or following excision of the primary tumor. In contrast, male BALB/c mice inoculated with a Ki-MuSV-transformed clonal line (KB521) exhibited 44 and 37% incidence of pulmonary metastasis with the growing tumor or following excision of the primary tumor, respectively. An independently derived clone of Ki-MuSV-transformed Balb/3T3 (K234) and its subclone (KA31) exhibited faster tumor growth rate, higher percent tumor cell take, and no spontaneous regression. These cell lines also showed a higher incidence, 67 and 100%, of spontaneous pulmonary metastasis with the growing primary tumor and following excision of the primary tumor, respectively. Expiant cultures of lung metastatic lesions from two metastatic lines also had fast tumor growth rate and a high incidence of spontaneous metastasis comparable to the parental cell of origin. The results indicated that differences in tumorigenic and metastatic properties of MuSV-transformed nonproducer cell lines could occur both as a result of oncogenic virus strain and/or variations in the target cell. MuSV nonproducer lines should be useful as model systems for the study of tumor metastasis.