tbuckley/cabot-search huggingface dataset:
Phase I study of NK105, a paclitaxel-incorporating micellar nanoparticle, in patients with advanced cancer
Authors: K. Kato, T. Hamaguchi, H. Yasui, T. Okusaka, H. Ueno, M. Ikeda, K. Shirao, Y. Shimada, H. Nakahama, K. Muro, Y. Matsumura
Journal: Journal of Clinical Oncology (2006)

2018 Background: NK105 is a new polymeric micelle carrier system for paclitaxel (PTX). A preclinical study revealed that the plasma AUC and tumor AUC of NK105 were 90-fold higher and 25-fold higher, respectively, than those of free-PTX, i.e., the conventional PTX formulation. NK105 had higher in vivo antitumor activity and lower neurotoxicity than free-PTX. This phase I study was designed to examine the MTD, DLTs, recommended dose (RD) for phase II, and the pharmacokinetics of NK105. Methods: NK105 was administered as a 1-hour intravenous infusion every 3 weeks, without antiallergic premedication. The starting dose was 10 mg PTX equivalent/m 2 , and the dose was escalated according to the accelerated titration method. Results: To date, 17 patients (pts) have received the following doses: 10 mg/m 2 (n=1); 20 mg/m 2 (n=1); 40 mg/m 2 (n=1); 80 mg/m 2 (n=1); 110 mg/m 2 (n=3); 150 mg/m 2 (n=5); and 180 mg/m 2 (n=5). The tumor types treated included pancreatic (n=9), bile duct (n=5), gastric (n=2), and colonic (n=1) cancers. Neutropenia was the most common hematological toxicity. Grade 3 fever developed in 1 pt given 180 mg/m 2 . No other grade 3 or 4 non-hematological toxicity, including neuropathy, was observed. DLTs occurred in pts given 180 mg/m 2 (grade 4 neutropenia lasting for more than 5 days). This dose was designated as the MTD. Allergic reactions developed in only one pt at 180 mg/m 2 , who was sensitive to other drugs such as antibiotics anti-inflammatory. A partial response was observed in one pt with pancreatic cancer and pts with colonic and gastric cancer had stable disease. The Cmax and AUC of NK105 were dose dependent. The plasma AUC of NK105 at 180 mg/m 2 was approximately 30-fold higher than that of the conventional formulation of PTX. Conclusions: Accrual is ongoing at the 150 mg/m 2 dose level to determine the RD. DLT was Grade 4 neutropenia. NK105 produces prolonged high levels of PTX in plasma. A 1-hour infusion of NK105 every 3 weeks was feasible, well tolerated, and effective in patients with pancreatic cancer. Even after the long term usage, only grade 1 or 2 neuropathy was observed. NK105 will be evaluated in Phase II studies of patients with advanced pancreatic and gastric cancers. No significant financial relationships to disclose.
The big man
Authors: Colin Douglas
Journal: BMJ (2000)

In a small country with a new parliament there was a big man. The big man was quite important in the new parliament. In fact he was the leader. And long before that, when most people in the small country thought it didn't need a parliament, he had worked hard and talked to a lot of people to persuade them that it did.

So when the people voted they got a parliament. On its first day the Queen came to open it. Everyone cheered, and the …
What about asthma in tuberculosis patients
Authors: Haifa Zaibi, Leila Fekih, Iness Akrout, Eya Tangour, Hela Hassene, Dorra Greb, Sorraya Fenniche, Hajer Ben Abdelghaffar, Dalenda Belahbib, Momamed Lamine Megdiche
Journal: European Respiratory Journal (2011)

Introduction:  The association of asthma and tuberculosis is rare but may raise particular issues around patient management. The aim of this study was to evaluate the control of asthma in tuberculosis patients.   Patients and methods:  We describe a retrospective study, which included ten asthmatic patients with tuberculosis during the period between June 2001 and June 2010.   Results:  Five men and five women were included, mean age was 37 years. Seven of them had pulmonary tuberculosis and three had lymphatic nods tuberculosis.Two patients had mild asthma, seven had moderate asthma and only one had sever and corticosteroid-dependant asthma. Seven patients had controlled asthma when tuberculosis diagnosis was established. Asthma treatment was based on inhaled corticoids and long-action Beta-2-agonists. During anti-tuberculosis treatment tow patients developed near fatal asthma. Long-term stable asthma control was achieved over a time course of three to eight years.   Conclusion:  The association of asthma and tuberculosis can lead to potential therapeutic difficulties because of pharmacologic interactions between anti-tuberculosis therapies and treatments for asthma treatment. In addition, asthma following treatment for tuberculosis appears to be well controlled.
Impact of Chemotherapy Dose Intensity on Cancer Patient Outcomes
Authors: Gary H. Lyman
Journal: Journal of the National Comprehensive Cancer Network (2009)

Chemotherapy dose intensity represents unit dose of chemotherapy administered per unit time. Dose intensity can be increased or decreased through altering dose administered, time interval of administration, or both. Evidence supporting the importance of delivered chemotherapy dose intensity on clinical outcomes in patients with potentially curable malignancies comes from in vitro studies of cancer cell lines and abundant in vivo preclinical studies, in addition to retrospective and prospective clinical trials in both advanced and early-stage disease settings. Myelosuppression continues to represent the major dose-limiting toxicity of cancer chemotherapy, resulting in considerable morbidity and mortality along with frequent reductions in chemotherapy dose intensity, which may compromise disease control and survival. Several retrospective and prospective randomized trials have shown that reductions in the chemotherapy dose intensity established in efficacy studies may compromise long-term disease control and survival. Despite compelling data, surveys in the United States and elsewhere have reported that dose reductions and delays frequently occur in clinical practice, even in the potentially curative setting. Alternatively, an increase in dose intensity above standard may be achieved through either increasing the dose of individual agents (dose escalation) or compressing or shortening the treatment interval (dose-dense). In early studies, dose-dense schedules showed an increase in survival, whereas the benefit of dose escalation studies has been less consistent and may be accompanied by other dose-limiting toxicities. This article focuses on the rationale for delivering full chemotherapy dose intensity, the apparent reasons for failing to deliver optimal treatment, and available strategies for sustaining full chemotherapy dose intensity when indicated. The delivery of full chemotherapy dose intensity in patients with potentially curable malignancies should be considered a quality of care indicator in clinical oncology.
Inspector condemns “substandard” psychiatric hospitals in Ireland
Authors: Doug Payne
Journal: BMJ (2000)

The inspector of mental hospitals in the Republic of Ireland has strongly criticised the substandard condition of some of the country's long stay psychiatric accommodation. Dr Dermot Walsh's annual report highlights unacceptable conditions in specific institutions—including some patients having to share underwear and endure broken toilets and cold food. It also notes that it is “totally unacceptable” that as many as 300 inpatients with learning disabilities currently share such facilities with seriously ill psychiatric cases.

In the report the inspector noted that he had identified many of the problems before, with little effect—routine overcrowding, peeling walls, antiquated furnishings, and little or no recreational or rehabilitation facilities. Among his new findings are a shortage of psychiatric …
Interpersonal psychotherapy for depressed antepartum women: a pilot study
Authors: M G Spinelli
Journal: American Journal of Psychiatry (1997)

Antenatal depression, a substantial risk factor for postpartum depression, occurs in 10% of pregnant women, but no clinical treatment trials of antenatal depression exist. In an effort to establish treatment guidelines for depression during pregnancy, the author reports on a treatment program using interpersonal psychotherapy for antepartum depression.A 16-week open pilot trial conducted with 13 pregnant women who met DSM-III-R criteria for major depression.The women's mean depression ratings decreased significantly from week 0 to week 16 of the treatment program.Interpersonal psychotherapy for antepartum depression appears to be an effective alternative to pharmacotherapy in pregnancy. This study served as a pilot for an ongoing controlled clinical treatment trial.
A Multi-Observer Study Examining the Radiographic Visibility of Fishbone Foreign Bodies
Authors: S R Ell, A Sprigg, A J Parker
Journal: Journal of the Royal Society of Medicine (1996)

The use of plain radiographs to localize a suspected fishbone foreign body is the subject of controversy. Accordingly radiographs of 14 species of fishbone, impacted in a soft tissue phantom, were assessed by a series of observers from the ENT department (consultant surgeons, senior registrars and house officers). The agreement was assessed by graphical description of the data and tested by a Spearman's rank correlation test. The overall results showed that, for the clinician, radiography is very useful to detect the bones of: cod, haddock, lemon sole, cole fish, grey mullet and plaice; useful for red snapper, monk fish, gurnard and salmon; and unhelpful in detecting bones from herring, pike, mackerel and trout. The use of radiographs to locate these impacted fishbones can be rationalized in the light of these findings.
A phase 1b/2 study of LEE011 in combination with binimetinib (MEK162) in patients with <i>NRAS</i>-mutant melanoma: Early encouraging clinical activity.
Authors: Jeffrey Alan Sosman, Muaiad Kittaneh, Martijn P. J. K. Lolkema, Michael Andrew Postow, Gary Schwartz, Catherine Franklin, Alessandro Matano, Suraj Bhansali, Sudha Parasuraman, Kevin Kim
Journal: Journal of Clinical Oncology (2014)

9009 Background: NRAS-mutant melanoma has poor prognosis with no approved targeted therapies. Enhanced MAPK pathway signaling and cell cycle checkpoint dysregulation are frequent in NRAS-mutant melanoma. Thus, simultaneous inhibition of MEK and CDK4/6 could further suppress pathway activation. The MEK inhibitor binimetinib (MEK162) showed clinical activity in patients (pts) with NRAS-mutant melanoma. In preclinical studies, the selective CDK4/6 inhibitor LEE011 demonstrated tumor growth inhibition, and in combination with binimetinib led to regressions in NRAS-mutant melanoma models, warranting clinical study. Methods: This is a phase 1b/2, open-label study of LEE011 + binimetinib in pts with NRAS-mutant melanoma. The primary objective of the phase 1b part is to estimate the MTD/RP2D of the combination, using a Bayesian logistic regression model (BLRM) with overdose control. Secondary objectives include safety, pharmacokinetics (PK), and preliminary efficacy. LEE011 is administered once daily for 21 days of each 28-day cycle and binimetinib is administered twice daily continuously. Results: As of Dec 20, 2013, 14 pts were enrolled (93% stage M1c; ECOG PS 0/1/2 [43%/50%/7%]; median 2 prior lines) and were treated with LEE011 at 200 mg (dose level [DL] 1, n = 8) or 300 mg (DL 2, n = 6) and with binimetinib 45 mg. DLTs occurred at DL 1 (grade 3 acute renal injury, n = 1) and DL 2 (grade 4 asymptomatic creatine phosphokinase [CPK] elevation and grade 3 edema plus grade 4 atrial fibrillation, 1 pt each). Common treatment-related toxicities included CPK elevation, rash, edema, anemia, nausea, diarrhea, and fatigue. Preliminary PK was consistent with single-agent data for either drug, with no evidence of drug-drug interaction. Six pts achieved partial response (43%; 1 confirmed, 5 unconfirmed) and 6 had stable disease (4 with tumor shrinkage > 20%). Several pts experienced early tumor shrinkage with major symptomatic improvement; 8 pts remain on treatment (duration 2-8 mo). Conclusions: Combined LEE011 + binimetinib shows promising preliminary antitumor activity in pts with NRAS-mutant melanoma. Determination of a phase 2 dose and schedule and PD effects are ongoing. Clinical trial information: NCT01719380.
Concomitant radiotherapy and chemotherapy is superior to radiotherapy alone in the treatment of locally advanced anal cancer: results of a phase III randomized trial of the European Organization for Research and Treatment of Cancer Radiotherapy and Gastrointestinal Cooperative Groups.
Authors: H Bartelink, F Roelofsen, F Eschwege, P Rougier, J F Bosset, D G Gonzalez, D Peiffert, M van Glabbeke, M Pierart
Journal: Journal of Clinical Oncology (1997)

To investigate the potential gain of the concomitant use of radiotherapy and chemotherapy in improving local control and reducing the need for colostomy, a randomized phase III trial was performed in patients with locally advanced anal cancer.From 1987 to 1994, 110 patients were randomized between radiotherapy alone and a combination of radiotherapy and chemotherapy. The patients had T3-4NO-3 or T1-2N1-3 anal cancer. Radiotherapy consisted of 45 Gy given in 5 weeks, with a daily dose of 1.8 Gy. After a rest period of 6 weeks, a boost of 20 or 15 Gy was given in case of partial or complete response, respectively. Surgical resection as part of the primary treatment was performed if possible in patients who had not responded 6 weeks after 45 Gy or with residual palpable disease after the completion of treatment. Chemotherapy was given during radiotherapy: 750 mg/m2 daily fluorouracil as a continuous infusion on days 1 to 5 and 29 to 33, and a single dose of mitomycin 15 mg/m2 administered on day 1.The addition of chemotherapy to radiotherapy resulted in a significant increase in the complete remission rate from 54% for radiotherapy alone to 80% for radiotherapy and chemotherapy, and from 85% to 96%, respectively, if results are considered after surgical resections. This led to a significant improvement of locoregional control and colostomy-free interval (P = .02 and P = .002, respectively), both in favor of the combined modality treatment. The locoregional control rate improved by 18% at 5 years, while the colostomy-free rate at that time increased by 32% by the addition of chemotherapy to radiotherapy. No significant difference was found when severe side effects were considered, although anal ulcers were more frequently observed in the combined-treatment arm. The survival rate remained similar in both treatment arms. Skin ulceration, nodal involvement, and sex were the most important prognostic factors for both local control and survival. These remained significant after multivariate analysis. The improvement seen in local control by adding chemotherapy to radiotherapy also remained significant after adjusting for prognostic factors in the multivariate analysis. Event-free survival, defined as free of locoregional progression, no colostomy, and no severe side effects or death, showed significant improvement (P = .03) in favor of the combined-treatment modality. The 5-year survival rate was 56% for the whole patient group.The concomitant use of radiotherapy and chemotherapy resulted in a significantly improved locoregional control rate and a reduction of the need for colostomy in patients with locally advanced anal cancer without a significant increase in late side effects.
The cyclooxygenase theory of aspirin-induced asthma
Authors: A Szczeklik
Journal: European Respiratory Journal (1990)

Aspirin-induced asthma is a distinct clinical syndrome which affects about 10% of adult asthmatics. In these patients aspirin and several other analgesics precipitate asthmatic attacks. The idea that the attacks might result from the specific inhibition of a single enzyme, namely cyclooxygenase, has gained both experimental and clinical support. It stimulated a number of hypotheses on the mechanism of bronchoconstriction. All these hypotheses, here discussed, operate within the framework of the cyclooxygenase theory. Their major assumption is that inhibition of cyclooxygenase triggers specific biochemical reactions which lead to open asthma attacks.
Relapse following discontinuation of lithium maintenance therapy in adolescents with bipolar I illness: a naturalistic study
Authors: M Strober, W Morrell, C Lampert, J Burroughs
Journal: American Journal of Psychiatry (1990)

The authors conducted an 18-month naturalistic prospective follow-up study of 37 adolescents whose bipolar I illness had been stabilized with lithium carbonate during inpatient hospitalization. Thirteen of the patients discontinued prophylactic lithium therapy shortly after discharge. The relapse rate of bipolar illness in these 13 patients was nearly three times higher than the rate in patients who continued lithium prophylaxis without interruption. Early relapse among lithium-treated patients was associated with a greater risk of relapsing again. The authors discuss the theoretical and clinical implications of these findings.
Intrahepatic versus extrahepatic cholangiocarcinoma: Is there a difference in survival?
Authors: K. Ahmed, M. S. Beg, R. Komrokji, M. M. Safa
Journal: Journal of Clinical Oncology (2008)

15564 Background: Cholangiocarcinoma remains as a therapeutic challenge with surgery often being the only curative option. Recently, it has been described that patients with resectable tumors have median survival of 59 months versus 9 months in patients with unresectable disease. In this retrospective study, we analyze data comparing survival in intrahepatic cholangiocarcinoma (IHCC) versus extrahepatic cholangiocarcinoma (EHCC) across the Veterans Affairs (VA) Medical centers. Methods: The VA Central Cancer Registry (VACCR) is a function of the Chief, Program Office for Oncology at VA Headquarters in Washington DC. We queried the VACCR database for all diagnosed bile duct cancer cases between 1995 and 2005 using primary site code 221 (IHCC) and 240 (EHCC). The data was transformed, entered and analyzed using SPSS v.13.0. Patient and disease characteristics were compared using chi-square test. Overall survival was estimated with Kaplan-Meier method. Results: A total of 825 cases of cholangiocarcinoma were identified, of which 340 (41.2%) were IHCC and 485 (58.8%) were EHCC. Overall 122 (14.8%) patients were black (IHCC=52, 15.3%; EHCC=70, 14.4%; p=0.123). In those with IHCC, 78 (22.9%) had metastatic disease vs. 80 (16.5%) in EHCC (p<0.001). Surgery was more likely to be performed in EHCC than IHCC (26% vs. 9.1%; p<0.001). Median survival in EHCC was 5.97 months vs. 3.67 months in IHCC (p<0.001). Surgery significantly increased overall survival in both groups (table). Conclusion: IHCC and EHCC remain as therapeutic challenges. Surgical resection is the mainstay of therapy in VA patients with cholangiocarcinoma and has been shown to increase survival of these patients. Although surgical resection was performed more often in EHCC than IHCC, survival was similar in both if surgical resection was achieved. Surgery did increase overall survival in both groups. Overall Survival in IHCC and EHCC Survival (months) IHCC EHCC p-value All cases 3.67 5.97 <0.001 Metastasis 2.17 2.93 0.45 No Mets 5 6.57 0.374 Surgery 13.63 13.47 <0.001 No Surgery 3.13 4.4 <0.001 No significant financial relationships to disclose.
Chitosan-film enhanced chitosan nerve guides for long-distance regeneration of peripheral nerves
Authors: Cora Meyer, Lena Stenberg, Francisco Gonzalez-Perez, Sandra Wrobel, Giulia Ronchi, Esther Udina, Seigo Suganuma, Stefano Geuna, Xavier Navarro, Lars B. Dahlin, Claudia Grothe, Kirsten Haastert-Talini
Journal: Biomaterials (2015)

Biosynthetic nerve grafts are developed in order to complement or replace autologous nerve grafts for peripheral nerve reconstruction. Artificial nerve guides currently approved for clinical use are not widely applied in reconstructive surgery as they still have limitations especially when it comes to critical distance repair. Here we report a comprehensive analysis of fine-tuned chitosan nerve guides (CNGs) enhanced by introduction of a longitudinal chitosan film to reconstruct critical length 15 mm sciatic nerve defects in adult healthy Wistar or diabetic Goto-Kakizaki rats. Short and long term investigations demonstrated that the CNGs enhanced by the guiding structure of the introduced chitosan film significantly improved functional and morphological results of nerve regeneration in comparison to simple hollow CNGs. Importantly, this was detectable both in healthy and in diabetic rats (short term) and the regeneration outcome almost reached the outcome after autologous nerve grafting (long term). Hollow CNGs provide properties likely leading to a wider clinical acceptance than other artificial nerve guides and their performance can be increased by simple introduction of a chitosan film with the same advantageous properties. Therefore, the chitosan film enhanced CNGs represent a new generation medical device for peripheral nerve reconstruction.
Differences in Imiquimod treatment outcome in two patients with Bowenoid Papulosis containing either episomal or integrated HPV 16.
Authors: Els Meulemans, Ernst-Jan M. Speel, Georges Ph Lucker, David Creytens, Adrienne Van Geest, Ton Vermeulen, Sandra Claessen, Patrick Pauwels
Journal: Clinical Cancer Research (2006)

A61  Bowenoid papulosis (BP) is an intraepithelial neoplasia presenting with multiple, small, well-demarcated papillomatous papules or small patches on the vulva or penile shaft, glans or foreskin. High-risk mucosal HPV types are associated with BP, with HPV 16 most frequently detected. Common treatment modalities of BP include excision, circumcision, electrodessication, laser ablation, cryotherapy, photodynamic therapy, and local administration of 5-fluorouracil. Recurrence rates, however, are high and therefore improvement of therapies is needed. Imiquimod has proven effective in combating viral infections as well as UV-induced (pre) malignant lesions, and seems also effective in the treatment of BP.Because so far imiquimod treatment has not been related to the physical status of HPV, we present here two cases of intraepithelial neoplasia with papillomatous papules or small patches on the penile shaft, glans or foreskin with the clinical diagnosis of BP.For the first patient, histological examination revealed full-thickness epithelial dysplasia, supporting the clinical diagnosis of BP. Because these lesions may be associated with HPV, PCR amplification was performed on extracted DNA from these lesions. Infection with oncogenic HPV has been demonstrated, which turned out to be type 16 after EIA typing. FISH analyses showed diffuse staining of the cell nuclei suggesting the presence of the episomal form of the HPV virus in the lesion. Histology performed 1 month after treatment showed complete absence of epidermal dysplasia. These finding coincided with disappearance of the virus in the lesion, as revealed by PCR and FISH analysis. Nine months after discontinuations treatment no relapse was observed.For the second patient, histological examination of a skin biopsy revealed epithelial hyperplasia and dysplasia. This clinical and histological picture supports the diagnosis of BP. PCR amplification on genomic DNA from this lesion showed also infection with HPV type 16. Interestingly FISH analysis revealed two punctate signals per nucleus.In conclusion, imiquimod treatment provides a promising alternative therapy for BP. Complete cure might be expected when imiquimod treatment is applied to lesions in which HPV is still episomal and not integrated into the cellular genome. The recurrence risk, however, remains to be established and BP patients unresponsive to imiquimod should be evaluated carefully for the development of squamous cell carcinoma.