tbuckley/cabot-search huggingface dataset:
Mechanisms of Disease: An Introduction to Clinical Science, by Ed S Tomlinson, A M Heagerty, A P Weetman
Authors: E R Chilvers
Journal: BMJ (1997)

Ed S Tomlinson, A M Heagerty, A P Weetman: Cambridge University Press, £19.95, pp 513 ISBN 0 521 46738 1

Progress towards establishing a truly integrated medical curriculum in Britain that provides students with an adequate scientific base to support bedside clinical teaching and, more importantly, the capacity to continue to learn has been painfully slow. While the need for such an approach to learning—in which understanding the basis of disease replaces the more traditional didactic approach—has long been recognised, the lack of appropriate books has been a major stumbling block.

Mechanisms …
Primary therapy of Waldenström's macroglobulinemia with 2-chlorodeoxyadenosine.
Authors: M A Dimopoulos, H Kantarjian, D Weber, S O'Brien, E Estey, K Delasalle, E Rose, F Cabanillas, M Keating, R Alexanian
Journal: Journal of Clinical Oncology (1994)

PURPOSE To assess the activity of 2-chlorodeoxyadenosine (2CdA) as primary therapy for patients with Waldenström's macroglobulinemia. PATIENTS AND METHODS 2CdA was given to 26 consecutive, previously untreated and symptomatic patients with Waldenström's macroglobulinemia. Two courses were administered to outpatients at a dose of 0.1 mg/kg body weight per day for a 7-day continuous infusion using a portable pump through a central venous catheter. Responding patients were followed up without further therapy and were scheduled to receive two additional treatments with 2CdA on disease relapse. RESULTS Twenty-two of 26 patients responded to the 2CdA therapy (85%; 95% confidence interval [CI], 65% to 96%), including three patients who achieved a complete response and 19 patients who had a partial response. Treatment was well tolerated, with no acute hematologic toxicity. A marked and sustained reduction of CD4+ lymphocytes occurred in all patients and may have contributed to a fatal infection with disseminated herpes simplex in one patient. With a median follow-up of 13 months, five patients have relapsed and all re-treated patients have responded again to 2CdA. CONCLUSION 2CdA is highly active in previously untreated patients with Waldenström's macroglobulinemia. A limited program of treatment induced responses of good quality and long duration in more than 80% of patients.
Dangers of over-the-counter nitrofurantoin for urinary tract infection
Authors: Gloria Cristina Cordoba, Anne Holm, Lars Bjerrum
Journal: BMJ (2015)

Over-the-counter nitrofurantoin for self diagnosed uncomplicated cystitis should be considered with caution and may cause more harm than good.1

Firstly, for antibiotics to be given only to those who will benefit, suspected uncomplicated cystitis must be assessed by …
MCL1 in transgenic mice acts at specific stages of T cell differentiation and in response to stimulation
Authors: Jingang Gui, Karen Braley, Michael Pierce, Ruth Craig
Journal: Clinical Cancer Research (2007)

AACR Centennial Conference: Translational Cancer Medicine-- Nov 4-8, 2007; Singapore

C12 

MCL1 is an anti-apoptotic BCL-2 member that was identified based on increased expression during the induction of differentiation in human myeloblastic leukemia cells. Previous studies in MCL1 transgenic mice demonstrated moderate viability enhancement in cells of a variety of hematopoietic lineages, as assessed using pan-B, T, and myeloid markers. The present studies utilized differentiation-stage specific markers to determine whether the MCL1 transgene affects specific cells within the T cell lineage. Findings to date have revealed an increase in early T lineage progenitors in the thymus of transgenic mice. This was accompanied by an increase in cells at the early stages of thymopoiesis, including CD4-CD8- double negative cells expressing CD25 (alpha chain of interleukin-2 receptor) and CD4+CD8+ double positive cells. This increase in occurred despite the fact that the bone marrow of the transgenic animals did not exhibit a noticeably change in the expression of markers characteristic of hematopoietic stem cells. In addition, analysis of peripheral lymphocytes did not demonstrate a change in lineage distribution or in the B/T cell ratio, suggesting that homeostatic mechanisms keep in check the effects of enforced MCL1 expression. Strikingly, however, transgenic splenocytes exposed in vitro to anti-CD3/anti-CD28 to mimic antigen stimulation exhibited an increase in CD4+ cells producing IL-2. Taken together, these findings show that, in normal healthy transgenic animals, MCL1 acts at specific stages in the differentiation of hematopoietic cells as well as in cells responding to stimulation.
Safety profile and pharmacokinetics of SB010, an inhaled GATA-3-specific DNAzyme, in phase I clinical trials in healthy and asthmatic subjects
Authors: Ursula Homburg, Agnieszka Turowska, Jens Kuhlmann, Anke Müller, Jonas Renz, Joachim Bille, Harald Renz, Holger Garn
Journal: European Respiratory Journal (2013)

SB010 (a solution of the human GATA-3-specific DNAzyme hgd40) has been developed as a treatment for Th2-driven asthma. DNAzymes are single-stranded catalytic DNA molecules that bind and cleave target mRNAs. Aim of these trials was to investigate safety, tolerability and pharmacokinetics of orally inhaled SB010 in healthy subjects and asthmatic patients. We performed 3 Phase I trials: single and multiple applications in healthy subjects (trials 1, 2) and single application in stable allergic asthma patients with airway hyperresponsiveness (trial 3). All trials were performed as randomized, double-blind, placebo-controlled, parallel group (per dose level) dose-escalation trials in male subjects. SB010 was applied as nebulized solution in 6 dose levels (0.4 – 40 mg trial 1) or in 3 dose levels (5 – 20 mg trials 2+3). Adverse events (AE), vital signs, clinical chemistry, hematology, urinalysis, ECG, pulmonary function testing and overall tolerability were assessed in 108 subjects. Plasma concentrations were analyzed using a hybridization ELISA. AEs were of minor clinical relevance and fully reversible during the trials. Maximum plasma concentrations of hgd40 were detected within the highest dose groups: 1 hour after single and multiple administration in healthy subjects (29.2±20.6 ng/mL, 10.0±14.5 ng/mL); 0.75 h after single application in asthmatic patients (14.0±16.6 ng/mL), hgd40 was no longer detectable 12 h after administration. Overall, inhaled SB010 was well tolerated after single or multiple inhalation in healthy subjects or single inhalation in patients. Based on these results SB010 is currently evaluated in Phase IIa clinical trials.
The efficacy and cost-effectiveness of adjuvant therapy of early breast cancer in premenopausal women.
Authors: T J Smith, B E Hillner
Journal: Journal of Clinical Oncology (1993)

PURPOSE AND METHODS We used decision analysis to model the natural history of breast cancer in hypothetical cohorts of 45-year-old women receiving tamoxifen, chemotherapy, or combined therapy. We used recurrence and efficacy data from the Early Breast Cancer Trialists' Collaborative Group (EBCTCG), utility values from focus groups, and costs from clinic charges and Medicare data. RESULTS Tamoxifen alone provides minimal benefit in estrogen receptor-negative (ER-; 0.2 to 0.4 months) and modest benefit in receptor-positive (ER+; 3.5 to 5.2 months) cancer. Chemotherapy adds substantial benefit independent of receptor status (4.9 to 10.7 quality-adjusted months). In ER+ cancer, combined therapy adds an additional benefit (1.2 to 2.1 months) compared with chemotherapy alone. The incremental costs (United States dollars) necessary to add an additional year of life to the average woman ranged from $4,300 to $11,400 for tamoxifen alone for ER+ cancer, $4,900 to $11,400 for chemotherapy alone, and $14,800 to $33,100 for combined therapy. CONCLUSION In premenopausal early-stage breast cancer, chemotherapy adds substantial clinical benefit at a modest cost. Tamoxifen alone adds meaningful benefit only in ER+ cancer. Combined therapy is effective for all women, but is most beneficial and only cost-effective in ER+ women. If secondary effects of tamoxifen in reduction of cardiovascular and osteoporosis mortality are confirmed, then combined treatment may be optimal for all premenopausal women.
Significant delay in the introduction of systemic treatment of moderate to severe psoriasis: a prospective multicentre observational study in outpatients from hospital dermatology departments in France
Authors: A. Maza, M.A. Richard, F. Aubin, J.P. Ortonne, S. Prey, H. Bachelez, M. Beylot-Barry, C. Bulai-Livideanu, M. Lahfa, J. Nougué, X. Mengual, M. Le Moigne, V. Lauwers-Cances, C. Paul
Journal: British Journal of Dermatology (2012)

There is a low rate of systemic treatment usage in moderate to severe psoriasis.The primary objective of the present study was to assess the time period between lack of control of moderate to severe psoriasis with topical treatment or phototherapy as perceived by patients and the medical decision to introduce a systemic treatment.This was a prospective multicentre study, which included patients with moderate to severe psoriasis. A standardized questionnaire was completed by physicians and patients at the time the decision was taken to introduce a systemic treatment. The primary outcome was the duration of uncontrolled psoriasis, as estimated by the patient, prior to the introduction of systemic treatment. Factors associated with a delay in systemic treatment defined as > 2 years of uncontrolled psoriasis were assessed. The agreement between patients and physicians on the duration of uncontrolled psoriasis was estimated.The study included 142 patients. The mean age was 48 years, the mean Psoriasis Area and Severity index (PASI) was 18·5 and the mean Dermatology Life Quality Index (DLQI) was 12. The median duration of uncontrolled psoriasis estimated by patients and physicians was 3 years and 2 years, respectively. Factors associated with a delay in the introduction of systemic treatment as assessed by patients were fewer than three physician visits since psoriasis was uncontrolled [odds ratio (OR) 3·05; 95% confidence interval (CI) 1·29-7·21], Hospital Anxiety and Depression (HAD) scale < 10 (OR 2·83; 95% CI 1·19-6·71), continuous psoriasis evolution (OR 2·67; 95% CI 1·12-6·42), low consumption of topical treatment (OR 2·35; 95% CI 1·03-5·34).There is a significant delay in the introduction of systemic treatment in moderate to severe psoriasis. Patients with low level anxiety and limited use of healthcare resources appear to be at higher risk of experiencing long delays.
Isolated limb perfusion with high-dose tumor necrosis factor-alpha in combination with interferon-gamma and melphalan for nonresectable extremity soft tissue sarcomas: a multicenter trial.
Authors: A M Eggermont, H Schraffordt Koops, D Liénard, B B Kroon, A N van Geel, H J Hoekstra, F J Lejeune
Journal: Journal of Clinical Oncology (1996)

To determine the efficacy of isolated limb perfusion (ILP) with tumor necrosis factor-alpha (TNF) in combination with interferon-gamma (IFN) and melphalan as induction therapy to render tumors resectable and avoid amputation in patients with nonresectable extremity soft tissue sarcomas (STS).Among 55 patients with 30 primary and 25 recurrent sarcomas, there were 48 high-grade and seven grade 1 sarcomas (very large, recurrent, or multiple). The composition of this series of patients is unusual: 13 patients (24%) had multifocal primary sarcomas or multiple recurrent tumors; tumors were very large (median, 18 cm); and nine patients (16%) had known systemic metastases. IFN was administered subcutaneously on the 2 days before ILP with TNF, IFN, and melphalan. A delayed marginal resection of the tumor remnant was usually performed 2 to 3 months after ILP.A major tumor response was seen in 87% of patients and rendered the sarcomas resectable in most cases. Clinical response rates were as follows: 10 (18%) completes responses (CRs), 35 (64%) partial responses (PRs), and 10 (18%) no change (NC). Final outcome was defined as follows by clinical and pathologic response: 20 (36%) CRs, 28 (51%) PRs, and seven (13%) NC. Limb salvage was achieved in 84% (follow-up duration, 20+ to 50+ months). In 39 patients, resection of the tumor remnant (n = 31) or of two to eight tumors (n = 8) after ILP was performed; local recurrence developed in five (13%). When no resection was performed (multiple tumors or systemic metastases), local recurrences were frequent (five of 16), but limb salvage was often achieved as patients died of systemic disease. Regional toxicity was limited and systemic toxicity minimal to moderate with no toxic deaths. Histology showed hemorrhagic necrosis; angiographies showed selective destruction of tumor-associated vessels.ILP with TNF, IFN, and melphalan is a safe and highly effective induction biochemotherapy procedure that can achieve limb salvage in patients with nonresectable extremity STS. TNF is an active anticancer drug in humans in the setting of ILP.
Prognostic significance of bone marrow micrometastases in patients with gastric cancer.
Authors: K W Jauch, M M Heiss, U Gruetzner, I Funke, K Pantel, R Babic, H J Eissner, G Riethmueller, F W Schildberg
Journal: Journal of Clinical Oncology (1996)

BACKGROUND Monoclonal antibodies (mabs) against components of the cytoskeleton such as cytokeratins allow single disseminated epithelial carcinoma cells to be detected in the bone marrow. The aim of this study was to examine the prognostic relevance of these cells in patients with gastric cancer and to evaluate by multivariate analysis their predictive value compared with conventional risk factors. PATIENTS AND METHODS A total of 1 x 10(6) cells from bone marrow aspirates were screened immunoctochemically for the presence and absolute number of disseminated tumor cells using mab CK2 to cytokeratin component no. 18. Patients were monitored prospectively for 30.6 +/- 15.2 months. RESULTS Between one and 122 CK2-positive cells per 1 million mononuclear bone marrow cells were present in 95 of 180 patients (53%). A similar prevalence of 51% was found in curatively operated patients (55 of 109). Comparison with conventional prognostic risk factors showed a correlation of cell dissemination with pathohistologic tumor (pT) stage (P = .07) and Bormann classification (P = .022). Tumor-cell content in the bone marrow predicted disease-free and overall survival in curatively resected patients (P = .007 and P = .049, respectively). Multivariate analysis, which included established risk factors, showed that extent of tumor-cell dissemination was an independent prognostic parameter for disease-free survival in T1/2 tumors (P = .014; relative risk [RR], 1.84; 95% confidence interval [CI], 1.35 to 2.52), in intestinal type carcinomas according to Laurén (P = .008; RR, 1.62; 95% CI, 1.23 to 2.12), and in patients without lymph node involvement (P = .004; RR, 2.43; 95% CI, 1.22 to 4.82). CONCLUSION Presence of disseminated tumor cells in bone marrow is indicative of systemic disease even in early-stage gastric cancer. The extent of tumor-cell presence in bone marrow correlates with prognosis in curatively resected patients. Therefore, a positive bone marrow finding may be a selection criteria for adjuvant treatment because of minimal residual tumor load.
Acute stress reaction among victims of the 1999 Athens earthquake: help seekers' profile.
Authors: Georgios N Christodoulou, Thomas J Paparrigopoulos, Constantin R Soldatos
Journal: World Psychiatry (2003)

Natural disasters adversely affect the lives of large populations, disrupt their social network, and result in an enormous economic damage; consequently, they constitute a major traumatic experience with ensuing psychopathology (1-5). In the case of earthquakes, this has been repeatedly documented by various groups of investigators (6-18). However, research has dealt primarily with the long-term psychosocial consequences of earthquakes (6-18), while their immediate psychological effects have not been systematically investigated. Yet, early psychological reactions to stressful life events might be a herald for the eventual development of posttraumatic stress disorder (PTSD) (19,20), a frequently disabling and long-lasting condition.

Earthquakes constitute a common type of natural disaster in Greece. This is because Greece is in an area of high seismic activity. The earthquake which struck the Athens metropolitan area on September 7, 1999 had a magnitude of 5.9 on the Richter scale and was the second strongest over the last twenty years; actually, in certain residential areas, it caused large material and considerable human casualties. The main earthquake was followed by many after-shocks of a smaller magnitude that lasted for about a couple of weeks. The death toll rose to 152; in addition, more than 25,000 individuals were evacuated, mainly in tents close to their place of residence, and a few more thousands moved permanently elsewhere.

The main purpose of the present study was to assess the diagnosis of acute stress reaction according to the ICD-10 (21) criteria among individuals seeking help at a psychological support service for earthquake victims. An additional objective was to evaluate the effect of certain risk factors which may predispose to the development of acute stress reaction in disaster victims.
Role of Routine Imaging in Lymphoma
Authors: Nina D. Wagner-Johnston, Nancy L. Bartlett
Journal: Journal of the National Comprehensive Cancer Network (2011)

Patients with lymphoma commonly undergo routine imaging studies after treatment completion, yet the appropriate interval, duration, and modality of follow-up, and the overall efficacy of various approaches is unclear. Existing guidelines are vague and not evidence-based, and consequently, practice patterns are varied. Most surveillance approaches in lymphoma have focused on early detection of recurrence, with the hope of prolonged survival and potential cure. Concerns regarding the prognostic value of frequent scanning, cost-effectiveness, and long-term risks associated with prolonged radiation exposure have led many to question the role of routine imaging in this setting. Given the multiple lymphoma subtypes and the clinical heterogeneity of these entities, a single approach to follow-up may not be reasonable. Much of the available literature focuses on Hodgkin lymphoma, and may not be generalizable. Retrospective series show that most relapses are detected by signs and symptoms regardless of the imaging schedule. In summary, clinicians are still left with "expert opinion" to guide them. This article examines the available data outlining the role of surveillance imaging in lymphoma.
Features of carbohydrate metabolism in patients with COPD
Authors: Viacheslav Kobylyansky, Elena Soyustova, Turusina Nfnyana, Babadzhanova Gulnara, Yury Suntsov, Olga Pivovarova, Elena Kazanseva, Anna Sotnikova, Nosova Nina, Vasiliy Pokrovsky
Journal: European Respiratory Journal (2012)

Aim of the work – to evaluate carbohydrate metabolism in patients with COPD.

Materials and methods: In a randomized multicentral study cross evaluation of disease incidence in a group of patients with COPD (300 subjects) and diabetes mellitus 2 type (DM2) (400 patients) was performed. Sugar blood level was also analyzed by glucose tolerance test (GTT) in COPD patients in the age of up to 60 years with normal fasting sugar levels in a subgroup of nonobese patients (50 subjects) and in obese patients (17 persons). COPD patients did not receive steroid drugs or received them through inhalation in small doses, which were abolished 1-2 days before GTT. Population data served the control, and in GTT studies 45 patients within the age group up to 60 years with simple bronchitis and bronchial asthma were used as additional control, 30 of them were nonobese and 15 obese.

Results: In COPD patients DM2 incidence was 2.8 times above control data (p 0.05). At the same time in both nonobese and obese COPD patients GTT figures exceeded control data by 1.5 times (p<0.001) and 2 times (p<0.005) respectively.

Conclusion. COPD is an important risk factor in developing glucose tolerance disorders and DM2 and requires their purposeful diagnostics and correction.
Human Pulmonary Endothelial Cells in Culture
Authors: Alice R. Johnson
Journal: Journal of Clinical Investigation (1980)

Endothelial cells were cultured from various different human vessels, including aortas, pulmonary, ovarian, and umbilical arteries, and pulmonary, ovarian, and umbilical veins. The cultured cells were identified as endothelial cells by the presence of Factor VIII antigen and antiotensin I converting enzyme (kininase II). They retained these markers for at least five passages in culture, and some cells had them for seven passages or more. Endothelial cells from the various vessels were compared with respect to their ability to metabolize angiotensins I and II and bradykinin. Cells from arteries had three to five times the angiotensin I converting enzyme activity as cells from veins. The activity of angiotensinase A (aspartyl aminopeptidase) had a similar distribution, and cells from arteries were consistently more active than cells from veins. Cultures of endothelial cells from pulmonary and umbilical vessels formed prostacyclin in response to mechanical stimulation. Media from cell monolayers that were subjected to a change of medium and gentle agitation inhibited aggregation of human platelets. This inhibitory activity was generated within 2-5 min, and it was not formed by cells that were treated with indomethacin or tranylcypromine. Addition of prostaglandin (PG)H2 to indomethacin-treated cells restored the ability to form the inhibitor, but cells treated with tranylcypromine were not responsive to PGH2. In experiments where [14C]arachidonic acid was added to the cells before stimulation, the major metabolite identified by thin-layer chromatography was 6-keto PGF1α. Thus, it appears that pulmonary endothelial cells, as well as umbilical cord cells, can form prostacyclin. In experiments comparing the ability of arterial and venous cells to form prostacyclin, arterial cells were more active than venous cells. These studies of cells from various human vessels suggest that the vascular origin of cultured endothelial cells determines how they metabolize vasoactive peptides and form prostacyclin.
Author is lucky that his waiting list can be managed quickly
Authors: J. C McGregor
Journal: BMJ (1996)

Table 1-Self reported drug use and non-fatal overdose among 1018 drug injectors interviewed in Glasgow, 1993-4 Relative risk No (%) No (%) (95% confidence interval) Drug used or injected in using reporting compared with six months before Interview drug overdose rest of sample Injected heroin only 241 (24) 52 (22) 0.7 (0.5 to 0.9) Injected heroin and other drugs 661 (65) 213 (32) 2.2 (1.6 to 3.0) Injected drugs excluding heroin 116 (11) 11 (9) 0.3 (0.1 to 0.5) Methadone 453 (44) 132 (29) 1.2 (0.9 to 1.6)* Buprenorphine 413 (41) 109 (26) 0.9 (0.7 to 1.2)* Temazepam 793 (78) 244 (31) 2.7 (1.8 to 4.0) Cocaine 179 (18) 67 (37) 1.8 (1.3 to 2.5) Ecstasy 258 (25) 99 (38) 2.0 (1.5 to 2.8) *Not significant.