tbuckley/cabot-search huggingface dataset:
Paclitaxel by 3-hour infusion in combination with bolus doxorubicin in women with untreated metastatic breast cancer: high antitumor efficacy and cardiac effects in a dose-finding and sequence-finding study.
Authors: L Gianni, E Munzone, G Capri, F Fulfaro, E Tarenzi, F Villani, C Spreafico, A Laffranchi, A Caraceni, C Martini
Journal: Journal of Clinical Oncology (1995)

PURPOSE To define the maximum-tolerated dose (MTD) and better tolerated sequence of paclitaxel by 3-hour infusion plus bolus doxorubicin (DOX) and to evaluate antitumor efficacy. PATIENTS AND METHODS Thirty-five women with metastatic breast cancer (dominant visceral metastases in 56%, and involvement of &gt; or = three sites in 67%) who never received chemotherapy of any type were studied. Paclitaxel every 3 weeks (125 mg/m2 starting dose) was increased by 25-mg/m2 steps in subsequent cohorts of patients. DOX (60 mg/m2 fixed dose) was administered 15 minutes before the start of or after the end of paclitaxel for a maximum of eight cycles. Subsequently, patients in continuous response could receive single-agent paclitaxel (175 to 200 mg/m2 every 3 weeks). The drug sequence was alternated in consecutive patients and in the first two cycles. RESULTS Severe neutropenia that lasted greater than 7 days (n = 4), febrile neutropenia (n = 7) and grade III oral mucositis (n = 6) defined the MTD of paclitaxel at 200 mg/m2 in 34 assessable patients. Grade II peripheral neuropathy occurred in 33% of patients. Six women (18%) developed clinically reversible congestive heart failure (CHF) after a median of 480 mg/m2 total DOX. Drug sequence had no effect on toxicities. High efficacy on all metastatic sites in 32 assessable patients accounted for a 41% complete response (CR) rate (95% confidence interval [CI], 24% to 59%) and 94% overall-response rate (95% CI, 79% to 99%). After a median follow-up of 12 months (range 3 to 18), the median response duration is 8 months (range, 2+ to 18+) for complete responders and 11 months (range 1+ to 15+) for partial responders. CONCLUSION The rate of CR and incidence of CHF may be an expression of therapeutic and toxic enhancement due to the schedule used in this trial. Until clarification of this possibility, this promising combination should be used in investigational trials.
Jet-Lag and Shift Work: (1) Circadian Rhythms
Authors: J Waterhouse
Journal: Journal of the Royal Society of Medicine (1999)

Today it is commonplace for people to fly across several time zones on business or on holiday. Moreover, many people work at night rather than the conventional 9-to-5, not only to provide public services but also to use expensive equipment economically and engage in world-wide commerce. Both groups can experience ill-effects, known respectively as 'jet-lag' and 'shiftworker's malaise'l 4. In the short term, they feel tired and unable to concentrate, yet cannot sleep uninterruptedly during the night; they perform physical and mental tasks less well than usual and with more errors; they have no appetite and they experience indigestion or bowel upsets. As well as being troublesome at a personal level, these effects might have wider implications for example, by hampering international negotiations or reducing dexterity in a technical procedure. In the longer term also there are negative effects. For example, there is evidence for raised frequencies of menstrual disorders in airline hostessess and of gastrointestinal ulcers3 and cardiovascular morbidity in nightworkers6. A full explanation of these effects will doubtless indicate that the causes are complex and multiple, but a key issue is the 'body clock'. Here I outline its function and some of the non-pharmacological ways it can be influenced to alleviate jet-lag or shiftworker's malaise. The accompanying article by Arendt7 focuses on pharmacotherapy.
Failure to elicit seroresponses to pneumococcal surface proteins (pneumococcal histidine triad D, pneumococcal choline-binding protein A, and serine proteinase precursor A) in children with pneumococcal bacteraemia
Authors: A. Hagerman, K.M. Posfay-Barbe, S. Grillet, M.M. Ochs, R.H. Brookes, D. Greenberg, N. Givon-Lavi, R. Dagan, C.-A. Siegrist
Journal: Clinical Microbiology and Infection (2011)
Completion of treatment for latent tuberculosis infection
Authors: Claudia C. Dobler, Guy B. Marks
Journal: European Respiratory Journal (2011)

Background:  The effectiveness of latent tuberculosis infection (LTBI) treatment depends largely on adherence.   Aim:  To identify factors associated with patients9 completion of treatment for LTBI.   Methods:  We reviewed the characteristics of all patients who were prescribed a six month course of treatment with isoniazid for LTBI at the Chest Clinic of a large tertiary hospital between 01/2000 and 04/2008. A supply of isoniazid was dispensed one month at a time by Chest Clinic nurses. Treatment completion was defined as pickup of ≥ 80% of prescribed doses.   Results:  During the study period, 143 patients were started on this course of therapy. Their mean (SD) age was 25 (16) years and 43% were male. Seventeen patients were excluded from the analysis because their treatment was interrupted (n=4) or ceased (n=13) by their treating physician. Of the remaining 126 patients, 25 (20%) did not complete treatment. Treatment completion was not significantly related to patients9 sex, age, tuberculosis (TB) incidence in their country of birth, TST conversion status, smoking status, baseline liver function tests, or indication for treatment (contact versus other indications). However, among those who were contacts of a patient with active TB (n=102) those who were not living in the same household as the index case were more likely to fail to complete treatment (relative risk 7.2, 95% CI 2.6 to 20.7).   Conclusions:  In this cohort, with monthly supervision of drug collection, 1 in 5 patients who commenced treatment for LTBI did not complete their course of treatment. Non-household contacts of patients with active TB are at an increased risk of not completing treatment. This group may require additional strategies to encourage treatment completion.
Relationship Between Size and Perfusion Rate of Transplanted Tumors&lt;xref ref-type="fn" rid="fn1"&gt;2&lt;/xref&gt;
Authors: Samuel Cataland, Carl Cohen, Leo A. Sapirstein
Journal: JNCI Journal of the National Cancer Institute (1962)

The blood flow to subcutaneous transplants of Mammary Carcinoma 755 and Sarcoma 180 was measured by the indirect technique of indicator fractionation with the use of radioactive rubidium-86. The smallest tumors showed the largest fractional uptake of indicator per gram of tissue. Tumors of increasing size had progressively lower fractional uptake of indicator. It is concluded that mass increased more rapidly than the blood supply in these transplanted tumors.
Insulin demand regulates β cell number via the unfolded protein response
Authors: Rohit B. Sharma, Amy C. O’Donnell, Rachel E. Stamateris, Binh Ha, Karen M. McCloskey, Paul R. Reynolds, Peter Arvan, Laura C. Alonso
Journal: Journal of Clinical Investigation (2015)

Although stem cell populations mediate regeneration of rapid turnover tissues, such as skin, blood, and gut, a stem cell reservoir has not been identified for some slower turnover tissues, such as the pancreatic islet. Despite lacking identifiable stem cells, murine pancreatic β cell number expands in response to an increase in insulin demand. Lineage tracing shows that new β cells are generated from proliferation of mature, differentiated β cells; however, the mechanism by which these mature cells sense systemic insulin demand and initiate a proliferative response remains unknown. Here, we identified the β cell unfolded protein response (UPR), which senses insulin production, as a regulator of β cell proliferation. Using genetic and physiologic models, we determined that among the population of β cells, those with an active UPR are more likely to proliferate. Moreover, subthreshold endoplasmic reticulum stress (ER stress) drove insulin demand–induced β cell proliferation, through activation of ATF6. We also confirmed that the UPR regulates proliferation of human β cells, suggesting that therapeutic UPR modulation has potential to expand β cell mass in people at risk for diabetes. Together, this work defines a stem cell–independent model of tissue homeostasis, in which differentiated secretory cells use the UPR sensor to adapt organ size to meet demand.
Menopause and Breast Cancer: Addressing the Secondary Health Effects of Adjuvant Chemotherapy
Authors: Patricia A. Ganz, Gail A. Greendale
Journal: Journal of Clinical Oncology (2001)

Article Tools EDITORIAL Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2001.19.14.3303 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11454876 Menopause and Breast Cancer: Addressing the Secondary Health Effects of Adjuvant Chemotherapy Patricia A. GanzxPatricia A. GanzSearch for articles by this author , Gail A. GreendalexGail A. GreendaleSearch for articles by this author Show More University of California, Los Angeles Schools of Public Health and Medicine, Jonsson Comprehensive Cancer Center, Los Angeles, CA https://doi.org/10.1200/JCO.2001.19.14.3303 First Page Full Text PDF Figures and Tables © 2001 by American Society of Clinical Oncology
Cholesterol embolization in renal allografts.
Authors: J E Bolander, C B Carter
Journal: Journal of the American Society of Nephrology (1996)

Renal cholesterol embolization has been well described for many years. It has only been reported in a small number of renal transplant recipients, however. Two instances of primary renal allograft nonfunction because of cholesterol embolization are reported. The source of the emboli was believed to be the donor's aorta. Cholesterol embolization must be considered in the differential diagnosis of primary renal allograft dysfunction. Additionally, care must be taken during evaluation and procurement procedures to help avoid this complication.
Tetrabenazine Treatment for Tardive Dyskinesia: Assessment by Randomized Videotape Protocol
Authors: William G. Ondo, Philip A. Hanna, Joseph Jankovic
Journal: American Journal of Psychiatry (1999)

Tetrabenazine, a monoamine depleter and dopamine receptor blocker, is used to treat several hyperkinetic movement disorders. The authors studied the use of tetrabenazine for tardive dyskinesia.Twenty patients with tardive dyskinesia (mean duration = 43.7 months) were videotaped before and after tetrabenazine treatment. Randomized videotapes were scored with the motor subset of the modified Abnormal Involuntary Movement Scale (AIMS) by raters blind to pre- or posttreatment status.One patient did not tolerate tetrabenazine owing to sedation. The remaining 19 were rated after a mean of 20.3 weeks at a mean tetrabenazine dose of 57.9 mg/day. There were significant improvements in mean scores on both the patient AIMS self-rating and the AIMS motor subset evaluated by the blind videotape raters. All 19 patients continued to take tetrabenazine after the study.Tetrabenazine was well tolerated and resulted in significant improvements in AIMS scores for patients with refractory tardive dyskinesia.
The association between the asthma control test and the asthma quality of life questionnaire in adult asthmatics
Authors: Aylin Ozgen Alpaydin, Mine Bora, Arzu Yorgancioglu, Aysin Sakar Coskun, Pinar Celik
Journal: European Respiratory Journal (2011)

Aim: Asthma control and quality of life are expected to be correlated. We aimed to evaluate the association of asthma control test (ACT) with asthma quality of life questionnaire (AQLQ) and guideline based control assessment. We also aimed to investigate the impact of therapy adjustment according to ACT score on AQLQ levels.

Methods: A total of 101 consecutive, stable asthmatic patients between 18 and 55 years were included in the study. ACT and AQLQ were administered, GINA based control assessment was performed. Based on ACT control status, treatment was adjusted by stepping down in controlled, stepping up in uncontrolled and some well controlled patients. In some controlled and well controlled patients no therapy adjustment was done. After 3-months ACT and AQLQ were repeated.

Results: Mean age of the patients (82 female) was 42±11. According to GINA 22% were controlled, 20% were partly controlled and 59% were uncontrolled. Median and range for ACT score was 20 (16-23), while mean AQLQ total score was 4.59±0.94. We determined a significant association between ACT and AQLQ activity, symptom and environmental stimuli domain scores and total score (r=0.651, 0.697, 0.348, respectively, p<0.001). ACT scores increased in the step-up group (p<0.001), however AQLQ total scores were not affected. We found ACT concordant with GINA recommended control classification in the first (kappa=0.511, 7.718) and third months (kappa=0.599, 7.912) (p<0.001 for both).

Conclusion: We determined an association between ACT and AQLQ. ACT was also found fairly concordant with GINA. However, treatment adjustment according to ACT was not found satisfactory in terms of quality of life.
Does lung volume reduction surgery improve chronotropic incompetence in chronic obstructive pulmonary disease (COPD) patients
Authors: Hilary Armstrong, Matthew Bartels, Byron Thomashow
Journal: European Respiratory Journal (2011)

Introduction:  Chronotropic Incompetence (CI), or an attenuated heart rate (HR) response to exercise, has been widely established as a predictor of mortality. CI is reduced in patients with Chronic Obstructive Pulmonary Disease (COPD), and Lung Volume Reduction Surgery (LVRS) is known to improve morbidity and mortality in patients with COPD.   Objectives:  We aimed to see if LVRS improves CI in patients with COPD by evaluating CI in maximal exercise testing before and after LVRS.   Methods:  A retrospective chart review was performed on 82 patients who had undergone LVRS at Columbia University Medical Center (CUMC) between January 1998 to October 2009. Patients had CPET within 2 months before LVRS after completion of rehabilitation and repeat testing 6 months after LVRS. PFTs and other analyses were concurrent with CPET. Comparisons were made with paired samples t-test.   Results:  The mean PFT and CPET variables for the 84 patients analyzed improved following LVRS. CI was markedly reduced in patients before LVRS, and showed improvement following LVRS. After LVRS, the resting HR decreased by 4±12 beats per minute (bpm) (p=0.007), the HR at peak exercise increased 5±14bpm (p=0.003), and the heart rate reserve increased 9±13bpm (p   Conclusions:  CI is very abnormal in patients with severe COPD before LVRS and is improved after surgery. This improvement is in agreement with the observed increase in exercise capacity and improvement in PFT. The mechanism of the improvement in CI is not clear, but may be related to the improvement in pulmonary mechanics seen after successful LVRS. Further investigation into the implications of this change in CI is needed.
Evaluation of the peripheral airway microstructure in children with cystic fibrosis (CF) using 3He magnetic resonance imaging
Authors: Erol Gaillard, Iain Ball, Kuldeep Panesar, Noor Al-Khathlan, Manjith Narayanan, Caroline Beardsmore, John Owers-Bradley
Journal: European Respiratory Journal (2012)

Background: Pathology and lung function studies show that small airways are affected early in CF lung disease. Due to the inaccessibility of the distal air spaces little research has been performed in this area. The lung microstructure can be studied using the relatively new technique of hyperpolarised noble gas magnetic resonance (3HeMR) scanning(1).

Study aims: To compare acinar airway size of children with CF with that of healthy controls.

Methods: In children with relatively mild CF lung disease 3HeMR was undertaken during breath-hold following inhalation of a bolus of hyperpolarised 3He gas mixture. A signal was obtained using the q-space technique(2). We applied Yablonskiy's acinar model(3) on the raw data to obtain the values for mean acinar duct diameter, R and mean alveolar sleeve depth, h. All children had spirometry and lung clearance index (LCI) measured.

Results: We studied 9 children (6-10y) with CF (FEV1: 97.6%predicted; SD ± 14.3) and 18 age-matched controls. LCI was elevated in all CF patients (median 10.7; range 9.1-12.9). Acinar duct diameters (438.4μm; SD ± 21.8) and alveolar sleeve depth (294.2μm; SD ± 60.3) were both significantly (p<0.05) larger compared to controls (404.3μm; SD ± 34.8 and 223.8μm; SD ± 38.5 respectively).

Discussion: 3HeMR is well tolerated in children from school age. We found that R and h, both surrogate values for acinar size, are larger in children with mild CF lung disease compared to healthy controls. 3HeMR may constitute a sensitive technique for investigating CF lung disease.

References: 

1.Narayanan M et al 2012 AJRCCM; 185:186

2.Shanbhag DD et al 2006 JMRI; 24:84

3.Yablonskiy DA et al 2002 PNAS; 99:3111.
Bone density and skeletal metabolism in patients with orthotopic ileal neobladder.
Authors: S Giannini, M Nobile, L Sartori, F Aragona, A Ruffato, L Dalle Carbonare, M Ciuffreda, L Liberto, W Artibani, A D'Angelo, G Crepaldi, F Pagano
Journal: Journal of the American Society of Nephrology (1997)

The interposition of a bowel segment as a bladder substitute into the urinary tract may result in impaired calcium metabolism. We studied 25 male patients (aged 45 to 77 yr) who had undergone a Vescica Ileale Padovana (VIP) reconstruction following cystectomy 29 to 75 mo before. Bone mineral density of the spine and femur was measured by dual x-ray absorptiometry. Blood and 24-h urine samples were analyzed for the main parameters of bone metabolism. Sixteen healthy men were enrolled as a control group. Although blood pH did not differ between patients and control subjects, VIP subjects showed lower levels of plasma HCO3- (P < 0.005) and higher serum chloride (P < 0.001). Bone alkaline phosphatase was higher (P < 0.001), and urine calcium, phosphate, and creatinine levels were lower in VIP patients (P < 0.01, P < 0.01, and P < 0.05, respectively). Bone mineral density at the femoral neck (P < 0.03) and Ward's triangle (P < 0.05) was decreased in VIP patients. When subdivided according to time since operation, patients who had the ileal neobladder implanted for a shorter period of time showed lower blood pH (P < 0.03) and urine calcium (P < 0.05) levels and higher urinary hydroxyproline (P < 0.02). Duration of the ileal neobladder was positively correlated with PTH (r = 0.46, P < 0.03) and blood pH (r = 0.47, P < 0.02). Furthermore, pH values were positively correlated with urine calcium (r = 0.48, P < 0.02). In conclusion, in patients with ileal neobladder, a mild metabolic acidosis is responsible for an increased bone turnover and lower bone mass. Moreover, a decrease over time in the absorption capacity of the ileal pouch might result in calcium malabsorption, which represents an additional risk factor for reduced bone mass in these patients.
High-Dose Melphalan With Autotransplantation for Refractory Multiple Myeloma: Results of a Southwest Oncology Group Phase II Trial
Authors: David H. Vesole, John J. Crowley, Rose Catchatourian, Patrick J. Stiff, David B. Johnson, Jeana Cromer, Sydney E. Salmon, Bart Barlogie
Journal: Journal of Clinical Oncology (1999)

PURPOSE: To evaluate high-dose melphalan followed by autologous stem-cell transplantation in patients with refractory multiple myeloma. PATIENTS AND METHODS: Multiple myeloma patients with alkylating agent or vincristine/doxorubicin/dexamethasone–refractory disease were eligible for the phase II multi-institutional Southwest Oncology Group trial S8993. Patients up to age 70 years were enrolled between April 15, 1991, and May 1, 1996. Patients without prior stem-cell collection were primed with high-dose cyclophosphamide (HD-CTX; 6 g/m 2 ) and granulocyte-macrophage colony-stimulating factor. After stem-cell procurement, patients received melphalan 200 mg/m 2 with autologous transplantation. Upon recovery from melphalan, patients were to receive interferon alfa-2b until relapse. RESULTS: Seventy-two patients were enrolled onto S8993; five were ineligible and one received no therapy. Of the 66 assessable patients, 56 patients underwent the transplant procedure; 54 were assessable for response and 56 for toxicity. The response to HD-CTX (n = 37) included three complete remissions (CRs; 8%) and five partial remissions (PR; 14%); response to melphalan (n = 54) included 16 CRs (30%) and 19 PRs (35%), for an overall CR and ≥ PR (n = 66; intent-to-treat) of 27% and 58%, respectively. Toxicities included six treatment-related deaths: two during HD-CTX and four during transplantation. The median progression-free survival (PFS) and overall survival (OS) durations on an intent-to-treat basis from transplant registration was 11 months and 19 months (95% confidence interval, 14 to 29 months), respectively. The 3-year actuarial PFS and OS rates were 25% and 31%, respectively. CONCLUSION: High-dose therapy with melphalan 200 mg/m 2 is feasible with high response rates (58% overall) and an OS of 19 months in patients with refractory multiple myeloma.
Evaluation of a novel internally controlled real-time PCR assay targeting the 16S rRNA gene for confirmation of Neisseria gonorrhoeae infections
Authors: C. Schabereiter-Gurtner, P. Hufnagl, G. Sonvilla, B. Selitsch, M.L. Rotter, A. Makristathis, A.M. Hirschl
Journal: Clinical Microbiology and Infection (2008)
End-of-life care in oxygen-dependent COPD and cancer: a national population-based study
Authors: Zainab Ahmadi, Staffan Lundström, Christer Janson, Peter Strang, Margareta Emtner, David C. Currow, Magnus Ekström
Journal: European Respiratory Journal (2015)

Chronic obstructive pulmonary disease (COPD) is the third leading cause of mortality worldwide [1], and is associated with high morbidity and poor symptom control for long periods of time as the disease progresses [2]. At the end of life, COPD patients have a symptom burden comparable to, and often greater than, that associated with cancer [3]. Comparison between COPD and cancer is relevant because cancer patients have well-established palliative care programmes. Despite having extensive and similar end-of-life (EOL) needs to cancer patients, studies report unrelieved symptoms and low referral rates to palliative care in advanced COPD patients [4]. COPD patients have a high symptom burden but receive less palliative care than cancer patients at the end of life <http://ow.ly/NchLv> The work was carried out at the Department of Respiratory Medicine, Blekinge Hospital, Karlskrona, and Lund University, Lund, Sweden. We thank Bengt Midgren (Department of Clinical Sciences, Division of Respiratory Medicine and Allergology, Lund University Hospital, Lund, Sweden) for his valuable insights, Greger Fransson (Palliative Care Services, Stockholms Sjukhem Foundation, Stockholm, Sweden) for database management, and all the physicians and nurses who collected the data and cared for the patients.
Smoking cessation intervention.
Authors: J Kastelik, A Fahim, M Redfearn, H Lydon, M Greenstone
Journal: Thorax (2008)

We read with interest the article by Aveyard et al 1 on behavioural support as an intervention for smoking cessation in primary care. There is evidence that behavioural support doubles the likelihood of smoking cessation.2 3 Aveyard et al conducted a random-ised controlled trial and compared basic behavioural support with weekly support as a form of smoking cessation intervention. They have reported a quit rate of 22.4% at 4 weeks …