tbuckley/cabot-search huggingface dataset:
Phase II study of weekly chemotherapy with paclitaxel and gemcitabine as second-line treatment for advanced non-small cell lung cancer
Authors: K. Mori, Y. Kamiyama, T. Kondo, T. Kodama
Journal: Journal of Clinical Oncology (2006)

17096 Background: Second-line chemotherapy has become almost routine in non-small cell lung cancer (NSCLC) patients (pts) with good performance status (PS). The availability of the new pharmacological agents opens up new possibilities for their use in pts who have retained a good PS following relapse or progression after first-line chemotherapy. Paclitaxel (PTX) and Gemcitabine (GEM) are among the most active new agents in NSCLC and are worth considering for second-line chemotherapy. In phase II study, we evaluated the tolerability and activity of the combination of weekly PTX and GEM in second-line treatment of NSCLC. Methods: PTX (100mg/m 2 ) and GEM (1000 mg/m 2 ) were administered on days 1 and 8 at every 3–4 weeks. A total of 40 pts (M/F, 27/13 pts; median age 59.3 years [33–75]; PS 0/1/2, 7/27/6 pts) were enrolled between October 2000 and July 2003. Results: The number of cycles conducted was 1 in 5 pts, 2 in 8 pts, 3 in 10 pts, and 4 in 17 pts (mean: 4). The final efficacy was PR in 13, NC in 26 and PD in 1 for a response rate of 32.5 % (95% CI: 18.0–47.0%). The median survival time was 41.7 weeks (95% CI: 28.5–54.7 weeks). The median time to progressive disease was 19 weeks. Hematologic toxicities observed included Grade 3 or 4 neutropenia in 60%, Grade 3 or 4 anemia in 20%, and Grade 3 or 4 thrombocytepenia in 10%. Non-hematologic toxicities were mild except Grade 3 diarrhea in 3 pts and Grade 3 pneumonitis in 2 pts. There were no toxic deaths. Conclusions: The combination of weekly PTX and GEM is a feasible, well-tolerated, and active scheme for second-line treatment of advanced NSCLC. No significant financial relationships to disclose.
P42 Cholestatic pregnancy alters cholesterol and lipid transport to the fetal circulation, affecting lipid metabolism of the fetus
Authors: G Papacleovoulou, A Milona, B Owen, E Jansen, C Williamson
Journal: Gut (2010)

Introduction Altered nutritional environment during intrauterine life may permanently affect tissue homeostasis of the fetus that can increase susceptibility of offspring to the development of disease in later life. Intrahepatic cholestasis of pregnancy (ICP) is a liver-specific disease of pregnancy that is characterised by increased bile acid (BA) levels in the maternal serum.

Aim We aimed to establish the effects of exposure of the fetus to increased BA levels as a result of maternal cholestasis in the mouse.

Method C57BL/6 mice were used for our studies (six mice/group). Cholestatic pregnancy was achieved with addition of 0.5% of cholic acid (CA) in the standard diet (ERD) 1 week before mating and up to day 18 of gestation when animals sacrificed. Biochemical measurements and gene and protein expression analyses took place in the maternal and fetal serum as well as maternal liver, fetal liver and placenta.

Results Consistent with a cholestatic profile, fetuses from CA-fed mothers were characterised by raised BA levels in the serum (p<0.05). Also, the hepatic BA receptor, Fxr, was activated as indicated by alterations in its target genes (reduced Cyp7a1, increased Shp and Bsep). As a result of cholestasis, fetal hepatic cholesterol and fatty acid biosynthesis were induced as proved by up-regulation of Srebp2, Srebp1c, Hmgcr and Fas (p<0.05). Moreover, fetal hepatic cholesterol and triglycerides were increased relative to the levels of fetuses of ERD-fed mothers. Comparison between the placentas of ERD- vs CA-fed mothers revealed that CA-fed placentas had increased expression levels of lipogenic-related genes such as Adrp, Ldlr and Acat-2 (p<0.05), accompanied by raised placental cholesterol and decreased ApoB (p<0.05).

Conclusion Cholestatic pregnancy leads to fetal cholestasis and increased hepatic cholesterol and fatty acid biosynthesis. The placental gene expression and biochemical profile imply that cholesterol accumulates in placenta instead of crossing into the fetal environment. Therefore, increased fetal hepatic cholesterol and fatty acid biosynthesis could be an adaptive mechanism of the fetus to fulfil their developmental nutritional demands. This may have adverse effects in later life of the offspring.
A phase I dose-escalation clinical trial of a peptide-based human papillomavirus therapeutic vaccine with <i>candida </i>skin test reagent as a novel vaccine adjuvant for treating women with biopsy-proven cervical intraepithelial neoplasia 2/3.
Authors: Mayumi Nakagawa, Shawna L. Stratton, Rebecca Myrick, Rita Vaughn, Lisa M. Donnalley, Hannah Coleman, Maria Mercado, Andrea Moerman-Herzog, Horace J Spencer, Wilbur C. Hitt, Gordon Low, Nirvana Manning, Samantha McKelvey, Dora Smith, Michael Smith, Amy Phillips, C. Matthew Quick, Susanne K. Jeffus, Laura Fulper Hutchins, William Greenfield
Journal: Journal of Clinical Oncology (2015)

3032 Background: Non-surgical treatments for cervical intraepithelial neoplasia 2/3 (CIN2/3) are needed as surgical treatments have been shown to double preterm delivery rate. An investigational human papillomavirus (HPV) therapeutic vaccine, PepCan, consists of four current good manufacturing production-grade peptides covering the HPV type 16 E6 protein and Candida skin test reagent as a novel adjuvant. Methods: The study was a single-arm, single-institution, dose-escalation Phase I clinical trial, and patients with biopsy-proven CIN2/3 were eligible for vaccination. Four injections were administered intradermally every 3 weeks in limbs, and loop electrical excision procedure (LEEP) was performed 12 weeks after the last injection for treatment and histological analysis. Six subjects were enrolled at each dose level, and dose escalation was allowed as long as less than two subjects demonstrated dose-limiting toxicities. Results: Six subjects at each of four dose levels (50, 100, 250, and 500 mcg per peptide) were accrued, and none of the subjects experienced any dose-limiting toxicities. The most common adverse events were injection site reactions. Vaccine-induced immune responses to E6 were detected in 65% of recipients (significantly in 43%), and systemic T-helper type 1 (Th1) cells were significantly increased after 4 vaccinations (p= 0.02). The best histological response was seen at the 50 mcg dose level with a regression rate of 83% (n = 6), and the overall rate was 52% (n = 23). Conclusions: PepCan has been shown to be safe, and able to induce HPV-specific immune responses and Th1 cells. Candida, which has been shown in vitro to induce interleukin-12 secretion, is likely responsible for the increased Th1 cells, and should be considered as a candidate adjuvant for other vaccines. A Phase II clinical trial to assess the full effect of PepCan is warranted using the 50 mcg per peptide dose. Clinical trial information: NCT00569231.
Lesson of the Week: Failure of normalisation of (alpha) fetoprotein concentration after successful treatment of teratoma
Authors: H S Pandha, H S Wasan, K Harrington, J Waxman
Journal: BMJ (1995)

The development of successful treatment regimens for germ cell tumours has been one of the important advances in cancer chemotherapy. The effects of such treatment are monitored by measurement of serum concentrations of the tumour markers (alpha) fetoprotein and human chorionic gonadotrophin, as well as clinical and radiological assessment. The persistence of raised concentrations of (alpha) fetoprotein during or after treatment requires urgent investigation to delineate teratoma resistant to chemotherapy. We report on a patient with testicular teratoma who relapsed after initial chemotherapy in whom appreciably raised serum concentrations of (alpha) fetoprotein did not fall despite apparently successful salvage chemotherapy and surgery. An exhaustive search for a further residuum of disease was not fruitful. The finding of raised liver enzyme activities and hepatomegaly led to a liver biopsy, which showed alcoholic hepatitis. The patient decreased his alcohol intake, resulting in normalisation of his (alpha) fetoprotein concentration and liver enzyme activities.

A 37 year old man presented in May 1991 with testicular swelling and hepatomegaly. Orchiectomy was performed for an undifferentiated malignant teratoma that extended into the spermatic cord and blood vessels. Staging investigations showed para-aortic lymphadenopathy and a single lung metastasis. His concentration of human chorionic gonadotrophin was 1094 IU/l and of (alpha) fetoprotein 37 µg/l. Imaging studies showed no signs of liver metastases. His hepatomegaly was attributed to his alcohol consumption of 28 units a week and was accompanied by raised liver enzyme activities and a raised erythrocyte mean cell volume. He received four cycles of combination …
Guidelines for reporting of health interventions using mobile phones: mobile health (mHealth) evidence reporting and assessment (mERA) checklist
Authors: Smisha Agarwal, Amnesty E LeFevre, Jaime Lee, Kelly L’Engle, Garrett Mehl, Chaitali Sinha, Alain Labrique
Journal: BMJ (2016)

To improve the completeness of reporting of mobile health (mHealth) interventions, the WHO mHealth Technical Evidence Review Group developed the mHealth evidence reporting and assessment (mERA) checklist. The development process for mERA consisted of convening an expert group to recommend an appropriate approach, convening a global expert review panel for checklist development, and pilot testing the checklist. The guiding principle for the development of these criteria was to identify a minimum set of information needed to define what the mHealth intervention is (content), where it is being implemented (context), and how it was implemented (technical features), to support replication of the intervention. This paper presents the resulting 16 item checklist and a detailed explanation and elaboration for each item, with illustrative reporting examples. Through widespread adoption, we expect that the use of these guidelines will standardise the quality of mHealth evidence reporting, and indirectly improve the quality of mHealth evidence.
Gene expression levels of HER2 and IL-8 and polymorphism in IL-8 associated with clinical outcome in advanced or metastatic gastric cancer treated with lapatinib in SWOG 0413 trial
Authors: H. Chang, M. Azuma, B. Goldman, F. Nagashima, S. Iqbal, K. Danenberg, J. Benedetti, W. Zhang, C. Blanke, H. Lenz
Journal: Journal of Clinical Oncology (2007)

4647 Background: Lapatinib (GW572016) is a dual tyrosine kinase inhibitor of EGFR and HER2. In SWOG0413 trial, advanced or metastatic gastric cancer patients were treated with lapatinib. In this study, we investigated whether gene expressions and polymorphisms of EGF and angiogenesis pathway genes were associated with clinical outcome in the patients enrolled in SWOG0413 trial. Methods: A total of 46 patients were enrolled in SWOG0413 trial and treated with lapatinib. Blood and tissue samples were available from 42 and 37 patients, respectively. RT-PCR was performed for intratumoral gene expression levels of EGFR, HER2, VEGF, IL-8, COX2 and cyclin D1 genes. We also analyzed 8 polymorphisms in the EGF, EGFR, HER2, VEGF, IL-8, COX2 and cyclin D1 genes by PCR-RFLP. Results: Patients who have lower IL-8 [median overall survival (OS), 6 vs 3 months, p=0.03] and higher HER2 (6 vs 3 months, p=0.005) gene expression levels showed better OS. According to gene polymorphisms, patients who have A allele of IL-8 T251A polymorphism showed improved OS (A/A, 10 months vs T/A, 5 months vs T/T 3 months, p=0.04). And patients with A allele of IL-8 T251A and T allele of VEGF C936T polymorphisms showed better response rates (p&lt;0.01, p&lt;0.01, respectively). All other polymorphisms and gene expressions did not show significant association with clinical outcome. Conclusions: Our results suggest that intratumoral gene expression levels of HER2 and IL-8 and polymorphism in IL-8 are potential molecular predictors for survival in patients with advanced or metastatic gastric cancer treated with lapatinib. And polymorphisms in IL-8 and VEGF genes may be potential markers in predicting response in this population. A larger prospective study is needed to validate and confirm these preliminary findings. [Table: see text]
Abstract 13689: Right Ventricular Edema and Pericardial Effusion in Pulmonary Hypertension: Role of Lymphatics
Authors: Kelley L Colvin, Ozus Lohani, Michael E Yeager
Journal: Circulation (2015)

Introduction: Pulmonary hypertension (PH), regardless of etiology, is characterized by right ventricular remodeling and eventual failure. Pericardial effusion in the setting of PH is a serious and important clinical problem that portends a grim prognosis. Unfortunately, there are few mechanistic data available to explain its pathogenesis. Hypothesis: We hypothesized that the RV lymphatic vasculature and function would be decreased in PH associated with pericardial effusion. Methods: We examined human RV tissue from patients with PH and from rat models of PH with and without pericardial effusion and RV failure. We evaluated the extent of lymphatic vasculature, the presence of myocardial edema, and degree of pericardial effusion using invasive (immunoblot, immunohistology, RV wet/dry ratios) and non-invasive techniques (MRI, echocardiography, intravital imaging). To investigate whether neo-lymphangiogenesis affected RV function in PH, we treated rats with exogenous recombinant vascular endothelial growth factor C (VEGFC) before and during the development of PH. Results: We found decreased prox1+/podoplanin+ lymphatic vessels in RVs, but not left ventricles, from PH compared to either controls or to individuals with PH that lacked RV failure. The extent of lymphatic vasculature inversely correlated with the presence of myocardial edema, pericardial effusion, and positively correlated with cardiac output. In addition, the presence of increased interstitial fluid preceded development of RV fibrosis and was associated with increased numbers of tcf21+ RV fibroblasts. We found that administration of VEGFC induced a neo-lymphangiogenic response in RVs of rats, reduced myocardial edema, and promoted significant improvement in RV function. Conclusions: Decreased lymphatic vasculature and function likely contribute to myocardial edema and pericardial effusion in severe PH with RV failure. Augmentation of RV neo-lymphangiogenesis in rat models of PH greatly attenuated the edema, effusion, and fibrosis compared to vehicle controls. Collectively, these data raise the possibility that therapies to promote RV lymphangiogenesis and function may have important therapeutic benefit by reducing the high mortality of pericardial effusion in PH.
Review: Peripheral thermometers do not have clinically acceptable accuracy for measuring core body temperature
Authors: Harrison G. Weed
Journal: Annals of Internal Medicine (2016)

Source Citation Niven DJ, Gaudet JE, Laupland KB, et al. Accuracy of peripheral thermometers for estimating temperature: a systematic review and meta-analysis. Ann Intern Med. 2015;163:768-77. 26571241
Biweekly schedule of pegylated liposomal doxorubicin (PLD) induces low rates of skin toxicities: Results of a phase-II trial in heavily preteated patients with relapsed ovarian cancer
Authors: J. Sehouli, G. Oskay, I. Katsares, P. Klare, H. J. Hindenburg, G. Heinrich, B. Schmalfeld, D. Koensgen, W. Lichtenegger
Journal: Journal of Clinical Oncology (2004)

5072 Background: Pegylated liposomal doxorubicin ( PLD) formulation has been approved for the treatment of recurrent ovarian cancer (ROC). Toxic skin reactions were reported as being the dose-limiting toxicity and have an impact on patients' quality of life (QoL). The objective of this study was to optimize the toxicity profile by choosing a biweekly schedule of PLD according to the experience in patients with AIDS-related Kaposi sarcoma. A specific symptom check list was used to investigate QoL. Secondary objective of this study was to evaluate the response rates of this new regimen. Methods: We performed a multi-institutional phase-II study to analyze the toxicity profile of PLD (20mg/m2/q 14d) in patients (pts) with ROC. Eligibility criteria: ROC, prior treatment with platinum- and paclitaxel, ECOG status 0–2, organ functioning within normal range. Results: A total of 65 pts were recruited (10/2001–11/2003). 419 courses (median: 6, range: 1–22) were evaluable. Median age was 59 (35–80). Only 12 of the pts were in second-line, most of the pts were in third- or fourth-line. Nine pts were in fifth-line and one patient had 6 different prior regimens. Overall, the treatment was well tolerated. 24 pts developed skin toxicities: 15 pts with grade I, 5 with grade II and only 4 pts with grade III. These side effects occurred after a median of 6 courses. Heamatologic toxicity profile was favourable: no thrombocytopenia grade III/IV was observed. Only 3.2% episodes of lymphocytopenia grade III and 0.7% of grade IV occurred without clinical sequelae. Clinical response were evaluable by CA-125-monitoring and radiologic measurements. One patient developed a partial response, 24 ts developed a progressive disease after seven cycles (median) of treatment (range: 5–18). Conclusions: Despite the heavily pretreatment of the pts the results suggest that this new schedule seems to be an effective and well tolerated regimen, showing a low incidence of toxic skin reactions. The superiority over the conventional schedule must be clarified by a randomised trial. Supported by ESSEX Pharma Germany. No significant financial relationships to disclose.
Segmental allergen challenge increases levels of airway follistatin-like 1 in patients with asthma
Authors: Marina Miller, Stephane Esnault, Richard C. Kurten, Elizabeth A. Kelly, Andrew Beppu, Sudipta Das, Peter Rosenthal, Joe Ramsdell, Michael Croft, Bruce Zuraw, Nizar Jarjour, Qutayba Hamid, David H. Broide
Journal: Journal of Allergy and Clinical Immunology (2016)
Retrospective audit: depressive neurosis
Authors: S D Morrison
Journal: American Journal of Psychiatry (1977)

The charts of 100 patients with a primary diagnosis of depressive neurosis were subjected to retrospective audit using a format adapted from the American Psychiatric Association's Model Criteria Sets. Nineteen of the 33 unjustified variations from the audit criteria involved variations from the 8-28 day length of hospital stay. The author raises the question of whether the lower limit of 8 days is sufficiently flexible to permit hospitalization of acutely suicidal patients who can be discharged to outpatient care in less than 8 days.
A Comparison of Efficacy Between Recombinant Activated Factor VII (ARYOSEVEN TM) and NOVOSEVEN® in Patients with Hereditary FVIII Deficiency with Inhibitor
Authors: Mohammad Faranoush, Hassan Abolghassemi, Gh Toogeh, Mehran Karimi, Peyman Eshghi, M Managhchi, Hamid Hoorfar, Dehdezi B Keikhaei, B Mehrvar, Babak Khoein, K Kaymar, R Heshmat, Mohammad Baghaeipour, NB Mirbehbahhani, R Fayazfar, Majid Naderi, Minoo Ahmadinejad, F Mahbodi, Behrooz Vaziri
Journal: Blood (2014)
Posttraumatic stress disorder in elderly and younger adults after the 1988 earthquake in Armenia
Authors: A K Goenjian, L M Najarian, R S Pynoos, A M Steinberg, G Manoukian, A Tavosian, L A Fairbanks
Journal: American Journal of Psychiatry (1994)

This study was undertaken 1 1/2 years after the 1988 earthquake in Armenia to assess the frequency and severity of posttraumatic stress reactions among elderly and younger adult victims and to assess the relation of exposure, age, sex, and death of a family member to these reactions.One hundred seventy-nine subjects of both sexes were evaluated with the Posttraumatic Stress Disorder (PTSD) Reaction Index. A subgroup of 60 individuals were also assessed for PTSD with the DSM-III-R criteria.There was a strong association between the presence of severe symptoms on the index and a DSM-III-R diagnosis of PTSD. Elderly and younger adult victims in cities closer to the epicenter (higher exposure) had significantly higher index scores than elderly and adult victims in more distant locations. In comparison with previous studies of natural disasters, much greater rates of chronic severe posttraumatic stress reactions were found among the highly exposed individuals. Although there was no difference in total mean score on the Posttraumatic Stress Disorder Reaction Index, a significant difference in symptom profile was found between the elderly and younger adults; the elderly scored higher on arousal symptoms and lower on intrusive symptoms. There was a positive correlation between loss of family members and severity of posttraumatic stress reaction.These findings indicate that after a major natural disaster with subsequent multiple adversities, a substantial proportion of the adult population may experience severe and chronic posttraumatic stress reactions. The risk factors identified in this study may prove useful in screening exposed individuals for appropriate treatment.
Mind the gap: TB trends in the USA and the UK, 2000–2011
Authors: Chimeremma D Nnadi, Laura F Anderson, Lori R Armstrong, Helen R Stagg, Debora Pedrazzoli, Robert Pratt, Charles M Heilig, Ibrahim Abubakar, Patrick K Moonan
Journal: Thorax (2016)

<h3>Background</h3> TB remains a major public health concern, even in low-incidence countries like the USA and the UK. Over the last two decades, cases of TB reported in the USA have declined, while they have increased substantially in the UK. We examined factors associated with this divergence in TB trends between the two countries. <h3>Methods</h3> We analysed all cases of TB reported to the US and UK national TB surveillance systems from 1 January 2000 through 31 December 2011. Negative binominal regression was used to assess potential demographic, clinical and risk factor variables associated with differences in observed trends. <h3>Findings</h3> A total of 259 609 cases were reported. From 2000 to 2011, annual TB incidence rates declined from 5.8 to 3.4 cases per 100 000 in the USA, whereas in the UK, TB incidence increased from 11.4 to 14.4 cases per 100 000. The majority of cases in both the USA (56%) and the UK (64%) were among foreign-born persons. The number of foreign-born cases reported in the USA declined by 15% (7731 in 2000 to 6564 in 2011) while native-born cases fell by 54% (8442 in 2000 to 3883 in 2011). In contrast, the number of foreign-born cases reported in the UK increased by 80% (3380 in 2000 to 6088 in 2011), while the number of native-born cases remained largely unchanged (2158 in 2000 to 2137 in 2011). In an adjusted negative binomial regression model, significant differences in trend were associated with sex, age, race/ethnicity, site of disease, HIV status and previous history of TB (p&lt;0.01). Among the foreign-born, significant differences in trend were also associated with time since UK or US entry (p&lt;0.01). <h3>Interpretation</h3> To achieve TB elimination in the UK, a re-evaluation of current TB control policies and practices with a focus on foreign-born are needed. In the USA, maintaining and strengthening control practices are necessary to sustain the progress made over the last 20 years.
Effect of antihypertensive treatment on cognitive function of older patients
Authors: C D Irvine, S H Irvine
Journal: BMJ (1996)

# Effect is not proved {#article-title-2}

EDITOR,—On the basis of the results of two cognitive tests Martin J Prince and colleagues conclude that hypertensive drug regimens in elderly people impair cognition no more than does a placebo.1 This may lead to the changes suggested by the key message “Concerns about damaging cognition should not deter doctors from treating hypertension in older patients.” We have concerns about the study's design: the nature of the outcome measures used, the lack of any run in period before treatment to minimise practice …