tbuckley/cabot-search huggingface dataset:
Temsirolimus (TEM) in endometrial cancer: Predictors of response and progression.
Authors: R. A. Goodwin, R. Jamal, D. Tu, W. Walsh, J. Dancey, A. M. Oza, L. Elit, E. A. Eisenhauer
Journal: Journal of Clinical Oncology (2010)

3090 Background: NCIC CTG conducted a phase II trial of the mTOR inhibitor TEM in endometrial cancer since this tumor is associated with frequent PTEN loss. Our earlier work did not show a relationship between response (or progression) and PTEN or other molecular markers. Because of evidence that toxicity may relate to efficacy outcomes for EGFR inhibitors (Wacker, Clin Cancer Res 2007; Jonker, NEJM 2007), we explored the correlation between toxicity and outcomes in our trial. Methods: Response results (RECIST) in 60 treated patients (pts) (33 chemonaive) were 5 PR, 32 SD, 17 PD, and 6 IN. All pts receiving > 1 cycle of TEM (n = 49) were included. Prior chemotherapy and worst cycle 1 toxicity (see Table) were evaluated as potential predictors for partial response (PR) or progression (PD), as well as maximum % decrease from baseline tumor size (TS) in a univariate analysis (UA). Multivariate analysis (MVA) assessed UA variables significant at p<0.1. Results: No significant predictor was found for PR. Only prior chemotherapy was a significant, independent predictor by MVA for PD and TS: the adjusted odds ratio (OR) for PD was 7.37 (95% CI 1.32-41.03, p=0.02) and difference in TS was 24.4 (95% CI 3.94-44.8, p=0.03) between pts with/without prior chemotherapy. Conclusions: Pts with prior chemotherapy were more likely to have early PD and increase of tumor size. Similar to the TEM renal cell cancer study (deSouza, ASCO 2008) no relationship between efficacy outcomes and TEM-induced adverse events was demonstrated in this trial. Variable UA (p value) MVA adjusted OR (95%CI, p value) PR PD TS PR PD TS mean difference Categorical variables ≥ Gr 2 ANC 0.22 0.31 0.41 — — — ≥ Gr 2 mucositis 0.18 0.68 0.26 — — ≥ Gr 2 diarrhea 0.57 1.00 0.86 — — — Prior chemotherapy (Y/N) 0.15 0.003 0.02 — 7.37 (1.32 to 41.03, p=0.02) 24.4 (3.94 to 44.8, p=0.03) ≥ Gr 2 fasting triglycerides 0.40 1.00 0.28 — — — ≥ Gr 2 fasting glucose 0.08 0.64 0.08 — — −24.7 (−51.3 to 1.9, p = 0.08) ≥ Gr 2 fasting cholesterol 1.00 0.46 0.46 — — Continuous variables Highest triglyceride 0.85 0.17 0.11 — — — Highest cholesterol 0.99 0.06 0.45 — 0.76 (0.47–1.24, p = 0.27) — Highest glucose level 0.57 0.57 0.15 — — — Lowest ANC 0.22 0.04 0.13 — 1.56 (0.69–3.51, p = 0.28) — Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Wyeth
Children’s Health: Flu, Fetuses, and Schizophrenia
Authors: Julie Wakefield
Journal: Environmental Health Perspectives (2004)

Pregnant women who contract the flu may increase the risk that their child will develop schizophrenia later in life, according to a recent addition to a growing body of research along these lines. The study, published in the August 2004 Archives of General Psychiatry, “is not definitive but is the strongest evidence thus far that a prenatal virus may be a risk factor [for schizophrenia],” says lead investigator Ezra Susser, head of epidemiology at Columbia University’s Mailman School of Public Health.

“Influenza infection during pregnancy appears to be a risk factor,” agrees Johns Hopkins University neurovirologist Robert Yolken, who adds it is probably one of many risk factors for developing schizophrenia. The severe mental illness, which usually involves delusions, hallucinations, and disordered thinking, affects about 1% of the U.S. population. The Mailman team’s work is part of a larger study designed to examine prenatal infection and such factors as father’s age and prenatal exposure to chemicals in influencing schizophrenia in adulthood.

The Mailman team looked for influenza antibody in archived blood samples from 64 women whose children developed schizophrenia as adults and a control group of 125 women whose children did not develop the disorder. The samples were collected as part of the Child Health and Development Study, which collected blood samples from more than 12,000 mothers of children born between 1959 and 1967 and followed the children’s development into adulthood.

The risk of schizophrenia was tripled when the mother had the flu during the first half of pregnancy and increased sevenfold if exposure occurred in the first trimester. The overall risk is small, however. The findings suggest that about 97% of children born to women who got the flu while pregnant will not develop schizophrenia.

Although researchers do not know the mechanism of action, the Mailman team speculates that antibodies released by the mother’s immune system may affect the developing brain. But direct effects from the flu virus are also possible.

Researchers believe schizophrenia may result from a combination of genetic and environmental factors, including complications during delivery and exposure to the herpes simplex virus type 2 and to rubella virus during pregnancy. “It may not be just one virus,” Yolken says. “And [the key environmental factor] may vary from population to population, as genetic factors likely play a role.” Moreover, different strains of herpes or flu viruses may play greater or lesser roles.

Until more study is completed, the Mailman team still advocates that pregnant women get the flu shot. Susser says, “The very safest thing would be to get vaccinated against the flu virus before becoming pregnant.”
Reference value of six-minute walking distance in healthy Pakistani subjects
Authors: Nisar Rao, Muhammad Irfan, Suleman Haque, Ali Zubairi
Journal: European Respiratory Journal (2011)

Background:  Six-min walk test (6MWT) is useful in assessing functional exercise capacity. We aimed to determine the 6MWD for healthy Pakistanis, identify factors affecting 6MWD and derive an equation.   Methods:  15-65yrs subjects were prospectively enrolled after screening. A standardized 6MWT was administered. SpO 2 , HR, BP and dyspnea scores were determined pre and post-test.   Results:  296 subjects [211 (71%) men] participated with mean age 37.3±12 yrs. The mean 6MWD for all participants was 469.88±101.24m (range 180m - 756m) [men 502.35±92.21m; women 389.28±74.29m]. On univariate analysis gender, weight, height and age showed a significant relationship with the 6MWD. Sub analysis revealed a significant direct relationship between height (r=0.485, p=0.001) and weight (r=0.212, p  The regression equation predicting 6MWD is: y = β 0  + β 1 X 1  + β 2 X 2  + β 3 X 3  + ɛ  With an intercept term (β 0 ), slope parameters (β 1 , β 2 , β 3 ), one dichotomized variable of gender (X 1 , X 1 = “0” if the subject is female, and “1” if male).  The sex-specific prediction equations are:  6MWD (m) for men = 164.08 + (78.06$*$1) – (1.90$*$age) + (1.95$*$height)  6MWD (m) for women = 164.08 – (1.90$*$age) + (1.95$*$height)  Comparison with published equations revealed a moderate overestimation of the 6MWD in our population.   Conclusions:  6MWDs among Pakistanis are shorter than predicted by reference equations in literature. The proposed equation gives predicted (mean) 6MWDs for adult Pakistani naive to the test when employing standardized protocol. Prospective validation of this equation need larger community based studies.
Seven UK medical students studying in Sudan may be heading for Syria
Authors: D. Gardham
Journal: BMJ (2015)

On Monday 29 June it emerged that seven British medical students have flown to Turkey from Sudan seeking to join the militant group the Islamic State of Iraq and Syria.

They seem to be following in the footsteps of a group of five British people from the same university who crossed the border to Syria in March.

The first group also …
Indian hospital’s insensitive treatment of woman with HIV is condemned
Authors: Sanjeet Bagcchi
Journal: BMJ (2015)

The treatment of a 30 year old pregnant woman with HIV at a hospital in India has been criticised by experts and health organisations across the country.

The woman went to the Lala Lajpat Rai Memorial Medical College in Meerut to deliver her baby by caesarean section, and a sign indicating that she had HIV, with an “AIDS ribbon” drawn on it, was pasted to her bed. 

The woman was infected with HIV by her husband and decided to keep the matter secret. Her friends and family members found out that she had HIV while she was in the hospital, which left them in “shock.” The woman was asked to clean up …
Diffusing capacity for carbon monoxide (DLco) may predict appearance of pulmonary hypertension in idiopathic pulmonary fibrosis
Authors: Mitsuo Otsuka, Yasuo Kitamura, Keiki Yokoo, Kimiyuki Ikeda, Makoto Shioya, Hirotaka Nishikiori, Masanori Shiratori, Hiroki Takahashi
Journal: European Respiratory Journal (2013)

Rationale: Pulmonary hypertension (PH) is frequently complicated in the natural course of idiopathic pulmonary fibrosis (IPF) and the complication makes its prognosis poor. In order to search non-invasive and concise markers predicting onset of PH, we investigated the relationship between data on echocardiography and clinical parameters including pulmonary function tests.  Methods: From September 2009 to November 2012, we retrospectively investigated 67 patients with IPF in comparison with 11 with fibrotic NSIP (fNSIP). Tricuspid regurgitation pressure gradient (TRPG) > 30 mmHg determined by echocardiography was considered as PH in this study.  Results: PH was complicated more in IPF (27/67, 40%) than in fNSIP (2/11, 18%). TRPG was significantly correlated to %VC, %DLco and AaDO2. In IPF, patients with PH showed significantly lower %VC and %DLco, higher AaDO2, and poorer survival than patients without PH. Multivariate analysis showed TRPG and %VC were independent predictors of prognosis. Eighteen of 27 IPF without PH were subjected to the second echocardiography during 1 to 2 years after the first time. Five (28%) of the 18 IPF had newly developed PH and showed significantly lower %DLco at the first time and poorer survival than 13 IPF without newly developed PH.  Conclusions: PH, complicated frequently with IPF patients, is a poor prognostic factor. %DLco is a potentially useful non-invasive marker for early detection of PH.
Osteo-Arthrosis: Prevalence in the Population and Relationship between Symptoms and<i>X</i>-ray Changes
Authors: J. S. Lawrence, J. M. Bremner, F. Bier
Journal: Annals of the Rheumatic Diseases (1966)

Molyneux, 1966). Duthie, on the other hand, has found no evidence of any climatic influence.Cobb, Merchant, and Rubin (1957) observed that pain and swelling in osteo-arthrosic joints were seldom found without morning stiffness and that persons with x-ray evidence of osteo-arthrosis but no morning stiffness had only a small chance of having pain at the relevant site.They suggested that most of the symptoms of osteo-arthrosis are at least in part due to a rheumatoid component.Kellgren (1961) suggested that some of the painful episodes in this condition may be due to a ligamentous sprain or traumatic synovitis following minor injury to a joint rendered unstable by the disease.In the present paper the prevalence of osteo- arthrosis in populations in Northern England is reported and its relationship to symptoms in the region of the joints investigated.
Use of mental health services by US children and teens rises
Authors: M. McCarthy
Journal: BMJ (2015)

The proportion of children and teens receiving outpatient mental health services in the United States has risen markedly in recent years, a new study has found. But most of the use was by youths with less severe or no mental health impairment, while more than half of youths with more severe impairment went without needed care.

Researchers, led by Mark Olfson of Columbia University, NY, analyzed data from the Medical Expenditure Panel Surveys, which are nationally representative surveys of US households.1 They looked for trends in the outpatient use of …
Peripheral blood quantitative PCR analysis of EBV DNA in nasopharyngeal carcinoma
Authors: E. Sirachainan, N. Trachu, Y. Wisetpanit, R. Panvichian, A. Ratanavila, U. Udomsubpayakul, C. Chintrakarn, T. Sirisinha, T. Ativitavas, V. Ratanatharathorn
Journal: Journal of Clinical Oncology (2006)

5557 Background: Epstein-Barr virus (EBV) is the major etiology of WHO type 2, 3 nasopharyngeal carcinoma (NPC). Almost every tumor cell contains EBV genome. Correlation between prognosis, disease status and serum EBV DNA level was recently reported. Methods: We conducted a cross-sectional study to determine the correlation between the EBV DNA level from circulating tumor cells and the status of disease. The subjects were classified into 4 groups: new diagnosis, in remission, recurrent disease and control (healthy volunteers). The number of subjects/group was calculated to be at least 32, using proportion of P 0 = 40%, P 1 = 10% at α = 0.05 and Power = 80%. Genomic DNA was isolated from buffy coat of peripheral blood sample. Using Taqman probes for latent membrane protein 2 (LMP2) gene in EBV genome and beta actin gene as internal control, real-time quantitative PCR was performed. The LMP2 copy number was adjusted according to the beta actin copy number from the same sample. Results: The LMP2 gene can be quantified in the samples from new diagnosis, in remission, recurrent disease and control groups as following: 11/33 (33.3%), 10/29 (34.5%), 19/33 (57.6%) and 0/32 (0%) respectively. Among the patients with measurable LMP2, the median (range) of LMP2 copy numbers of each patient group are 12.97 (1.89–118.41), 18.75 (11.79–92.08) and 38.26 (2.41–642.76) copies/500 ng DNA respectively. Using Chi-Square test, all three patient groups have significantly higher LMP2 copy number than the control group (p &lt; .001). The recurrent disease group has significantly higher LMP2 copy number than the new diagnosis group (p=.048). There is no significant difference between the in remission group and the other patient groups. The sensitivity of this test is 42.1% and the specificity is 100%. Conclusions: The peripheral blood EBV DNA copy number, determined by Real-time quantitative PCR, may be a potential molecular marker in the screening for NPC. No significant financial relationships to disclose.
Antibiotic resistance pattern and clinical outcomes in acute cholecystitis: 567 consecutive worldwide patients in a prospective cohort study
Authors: Federico Coccolini, Massimo Sartelli, Fausto Catena, Giulia Montori, Salomone Di Saverio, Michael Sugrue, Marco Ceresoli, Roberto Manfredi, Luca Ansaloni
Journal: International Journal of Surgery (2015)
Capecitabine and thalidomide in previously treated, refractory metastatic colorectal cancer
Authors: A. D. McCollum, B. Wu, J. Clark, M. Kulke, P. Enzinger, D. Ryan, C. Earle, A. Michelini, C. Fuchs
Journal: Journal of Clinical Oncology (2004)

3657 Background: The survival of patients (pts) with metastatic colorectal cancer (CRC) has increased recently with the introduction of newer agents. Yet, there remains a need for more effective second- and third-line therapy. We conducted a phase II study to examine an oral combination regimen, capecitabine and thalidomide (Cape/Thal), in patients with previously treated, refractory metastatic CRC. Methods: Patients with stage IV CRC who had received one or more prior chemotherapy regimens were eligible. Treatment consisted of capecitabine at 1,000 mg/m2 po BID for 14 days every 3 weeks and thalidomide starting at 200 mg po daily continuously. Thalidomide was escalated individually to 600 mg po daily as tolerated. We analyzed overall survival (OS) and progression-free survival (PFS) along with response and toxicity rates. Results: Thirty-four eligible patients were enrolled: median age = 57 (35–73), M/F = 24/10, ECOG PS 0/1 = 22/12. All patients had recieved prior chemotherapy and 19 pts (56%) had received 2 or 3 prior regimens. The median number of Cape/Thal cycles administered was 3 (range: 1–15). Treatment was well tolerated; grade 3/4 toxicities included fatigue (15%), venous thromboembolic events (15%), somnolence (12%) and constipation (9%). Grade 2 hand-foot syndrome occurred in 5 pts (15%). There were no radiographic responses, but 5 pts (17%) acheived a decline in serum CEA of 50% or greater and 13 pts (38%) acheived stable disease. The median PFS was 2.6 months (95% confidence interval [CI] = 2.2–3.9) and the median OS was 7.1 months (95% CI = 5.2–12). Conclusions: The combination of capecitabine and thalidomide was well tolerated in this patient population. Despite the lack of radiographic responses, the rate of disease stabilization and overall survival observed in this heavily pre-treated cohort suggests that this regimen may offer some clinical benefit. No significant financial relationships to disclose.
Clinical impact of a highly prevalent Pseudomonas aeruginosa clone in Dutch cystic fibrosis patients
Authors: A.M.M. de Vrankrijker, R.W. Brimicombe, T.F.W. Wolfs, H.G.M. Heijerman, R. van Mansfeld, F.T. van Berkhout, R.J.L. Willems, M.J.M. Bonten, C. K. van der Ent
Journal: Clinical Microbiology and Infection (2010)
Multiple Sclerosis
Authors: H. Miller, A. Ridley, K. Schapira
Journal: BMJ (1960)

oedema, but that it will protect the patient against the known hazard of hypokalaemia associated with the use of hydrochlorothiazide.We thank the New Zealand Medical Research Council for making it possible for one of us (R. 0. F.) to participate in this trial.Spironolactone (" aldactone ") was kindly supplied by Dr. C.
Adaptive Evolution Is Substantially Impeded by Hill–Robertson Interference in<i>Drosophila</i>
Authors: David Castellano, Marta Coronado-Zamora, Jose L. Campos, Antonio Barbadilla, Adam Eyre-Walker
Journal: Molecular Biology and Evolution (2015)

Hill-Robertson interference (HRi) is expected to reduce the efficiency of natural selection when two or more linked selected sites do not segregate freely, but no attempt has been done so far to quantify the overall impact of HRi on the rate of adaptive evolution for any given genome. In this work, we estimate how much HRi impedes the rate of adaptive evolution in the coding genome of Drosophila melanogaster. We compiled a data set of 6,141 autosomal protein-coding genes from Drosophila, from which polymorphism levels in D. melanogaster and divergence out to D. yakuba were estimated. The rate of adaptive evolution was calculated using a derivative of the McDonald-Kreitman test that controls for slightly deleterious mutations. We find that the rate of adaptive amino acid substitution at a given position of the genome is positively correlated to both the rate of recombination and the mutation rate, and negatively correlated to the gene density of the region. These correlations are robust to controlling for each other, for synonymous codon bias and for gene functions related to immune response and testes. We show that HRi diminishes the rate of adaptive evolution by approximately 27%. Interestingly, genes with low mutation rates embedded in gene poor regions lose approximately 17% of their adaptive substitutions whereas genes with high mutation rates embedded in gene rich regions lose approximately 60%. We conclude that HRi hampers the rate of adaptive evolution in Drosophila and that the variation in recombination, mutation, and gene density along the genome affects the HRi effect.
Treatment of Recurrent Malignant Sacrococcygeal Germ Cell Tumors: Analysis of 22 Patients Registered in the German Protocols MAKEI 83/86, 89, and 96
Authors: D. T. Schneider, R. Wessalowski, G. Calaminus, H. Pape, M. Bamberg, J. Engert, K. Waag, H. Gadner, U. Göbel
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To evaluate therapeutic options for recurrent malignant sacrococcygeal germ cell tumors (GCT) following three-agent, cisplatinum-based, first-line chemotherapy and tumor resection. PATIENTS AND METHODS: Twenty-two patients were evaluated in 22 first-, 14 second-, five third-, and two fourth-relapse situations. One patient, who relapsed with pure teratoma, was excluded from the analysis of adjuvant treatment. RESULTS: Seventeen patients presented with an isolated local recurrence, two patients showed a distant relapse, and three patients suffered from a combined local and distant recurrence. Twelve patients achieved complete remission (CR) after surgery (n = 12) and adjuvant platinum chemotherapy (n = 10). Seven of these patients remain in continuous CR, and five patients relapsed. All patients who achieved only a partial remission developed a second relapse. Three of 14 patients could be cured after a second (or further) relapse. Altogether, 10 patients survived disease free, and 12 patients died as a result of tumor progression (n = 11) or therapy-related complications (n = 1). The completeness of salvage surgery and clinical remission status after first salvage treatment were the most important prognostic parameters. In addition, patients in first or second relapse with locally advanced or poorly responding tumors benefited from preoperative chemotherapy in combination with regional hyperthermia (RHT). In some patients after microscopically incomplete resection, irradiation at doses &gt; 45 Gy contributed to a favorable outcome. CONCLUSION: The complete resection of the local recurrence represents the cornerstone of salvage treatment. Preoperative platinum-based chemotherapy, combined with RHT in some patients, facilitates complete tumor resection. Radiotherapy should be reserved for those patients with microscopically incomplete tumor resection. As the chance of cure decreases with further relapses, it is important to establish a stringent therapeutic strategy to avoid significant treatment delays and, most importantly, insufficient local therapy.
Minichromosome Maintenance Protein 3 Elicits a Cancer-Restricted Immune Response in Patients with Brain Malignancies and Is a Strong Independent Predictor of Survival in Patients with Anaplastic Astrocytoma
Authors: Ariane Söling, Mirko Sackewitz, Michael Volkmar, Daniel Schaarschmidt, Roland Jacob, Hans-Jürgen Holzhausen, Nikolai G. Rainov
Journal: Clinical Cancer Research (2005)

Abstract Purpose: The identification of new molecular markers in astrocytic tumors may help to understand the biology of these tumors in more detail. Informative tumor markers may represent prognostic factors for response to therapy and outcome as well as potential targets for novel anticancer therapies. Experimental Design: Tumor-associated antigens were identified by immunoscreening of a human glioma cDNA expression library with allogeneic sera from patients with diffuse astrocytoma (WHO grades 2-4). The expression of one of the identified antigens, the replication licensing factor minichromosome maintenance protein 3 (MCM3), was analyzed by immunohistochemistry in 142 primary and 27 recurrent astrocytomas (WHO grades 2-4). In addition, 98 serum specimens from patients with primary and secondary brain malignancies and 30 serum specimens from healthy controls were examined by serologic immunoscreening for immunoreactivity with MCM3. Results: MCM3 is overexpressed in human astrocytic tumors and elicits a cancer-restricted humoral immune response in 9.3% (9 of 97) of patients with brain tumors (n = 95) and brain metastases (n = 2) but not in healthy controls. Expression of MCM3 in diffuse astrocytoma is significantly associated with age (P &amp;lt; 0.001), histologic grade (P &amp;lt; 0.001), time to recurrence (P = 0.01), and expression of the proliferation marker Ki-67 (P &amp;lt; 0.001) but not with sex (P = 0.800). Univariate and multivariate Cox regression analysis confirmed MCM3 expression as an independent predictor of poor outcome in astrocytoma patients (P &amp;lt; 0.001 for both). Conclusions: MCM3 may represent a glioma-associated antigen with significant prognostic role as well as have some potential as a target for cancer-directed therapy.