tbuckley/cabot-search huggingface dataset:
VP-16 and cisplatin as first-line therapy for small-cell lung cancer.
Authors: W K Evans, F A Shepherd, R Feld, D Osoba, P Dang, G Deboer
Journal: Journal of Clinical Oncology (1985)

Thirty-one patients with small-cell lung cancer (SCLC) were treated with VP-16 and cisplatin as first-line therapy. In the majority of cases an Adriamycin (Adria Laboratories, Columbus, Ohio) containing regimen was contraindicated because of severe cardiac or hepatic disease. Eight patients who presented with cerebral metastases were also included in the series. Eleven patients had limited disease (LD), and 20 had extensive disease (ED). Of the 28 evaluable patients, 12 (43%) achieved a complete response (CR) and 12 (43%) had a partial response (PR). Four patients (14%) either had no response or progressed on treatment. The median duration of response for patients with LD was 39 weeks and for those with ED, 26 weeks. The median survival time (MST) for the whole group of responding (CR and PR) LD patients was 70 weeks (range, 28 to 181 + weeks), and for responding ED patients, it was 43 weeks (range, 17 to 68 weeks). Gastrointestinal toxicity was mild, but leukopenia and thrombocytopenia were common. There were four febrile episodes during periods of drug-induced neutropenia and this led to one treatment-related death. Nephrotoxicity occurred in 15 patients and required discontinuation of cisplatin in two. These results compare favorably with reports of standard induction chemotherapy regimens and provide further evidence of the activity of the VP-16 and cisplatin regimen in patients with SCLC.
A phase II study of voreloxin as single agent therapy for elderly patients (pts) with newly diagnosed acute myeloid leukemia (AML)
Authors: M. B. Maris, F. Ravandi, R. Stuart, R. Stone, L. Cripe, M. Cooper, S. Strickland, F. Turturro, W. Stock, C. Berman
Journal: Journal of Clinical Oncology (2009)

7048 Background: Voreloxin is a naphthyridine analog that intercalates DNA and inhibits topoisomerase II, inducing apoptosis. Interim results of REVEAL-1, a phase II study of single agent voreloxin in newly diagnosed elderly AML pts, are reported. Methods: Phase II study of 3 voreloxin schedules (approximately 30 pts/schedule): A) 72 mg/m 2 qw x 3; B) 72 mg/m 2 qw X 2; or C) 72 mg/m 2 /dose on D1 and D4. Eligibility: newly diagnosed AML (de novo or secondary AML), pts age ≥ 60 and ≥ 1 additional adverse risk factor (age ≥ 70, secondary AML, intermediate or unfavorable cytogenetics, or PS 2). PK were evaluated in a pt subset in cycle 1. ex vivo sensitivity of pt BMA to voreloxin was evaluated by CellTiter-Glo proliferation assay. Results: Enrollment targets for schedules: A) (29) and B) (31) are met. Demographics (N = 54): 66% male, 35% female; median age 75 years; ECOG PS 0–1 90%, PS 2 10%. 20% AHD and cytogenetics were intermediate in 29%, unfavorable in 34%, and unknown in 36%. Final CR + CRp rate: A) 38%; B) too early to evaluate. Median duration of remission has not been reached. Thirty day all-cause mortality: A) 17%; B) 1 of 22, 4.5%. Infection was the most common cause of early mortality. Tolerability improved markedly in B): G3 or higher pneumonia (A 24%, B 11%) and mucositis (A 21%, B 11%) incidence were reduced. Voreloxin PK were similar to those in an earlier single agent phase I study in relapsed/refractory AML. C) enrollment is pending. Ex-vivo sensitivity did not predict clinical response. Conclusions: In REVEAL-1, voreloxin demonstrates clinical activity with 2 dosing schedules in previously untreated elderly (age ≥ 60) patients with AML who are unlikely to benefit from standard chemotherapy. CR + CRp rate was 38% (11 of 29 pts) for 3 weekly voreloxin doses (A). Early results from 2 weekly voreloxin doses (B) show 6 CR + CRp of 21 evaluable pts, with 2 pts in heme recovery, and improved tolerability. Enrollment to (C), voreloxin dosed D1 and D4, is pending. [Table: see text]
Mutations in the genes of drug-resistant mycobacterium tuberculosis in Uzbekistan
Authors: Nargiza Parpieva, Vera Beloserkoves, Khasan Safaev, Aziz Shakirov
Journal: European Respiratory Journal (2014)

Aim of research to study the prevalence of drug resistance in Mycobacterium tuberculosis circulating in various regions of Uzbekistan.

Materials and methods: In 2013 were tested 1438 patterns for drug susceptibility. The sensitivity of the MBT to anti TB drugs was determined using a diagnostic kit GenoType® MTBDR plus .

Results and discussion: Among the examined patient 793 (55%) were men, women were 645 (45%). By the instrumentality of a diagnostic kit GenoType® MTBDR plus in 40.4% (580) of patients identified sensitive strains of MBT to isoniazid (INH) and rifampicin (RIF). Mutations in the rpoB, katG, inhA genes were found in 59.6% (858) of patients. Mono-resistance to INH was detected at 13% (188) cases. Mono-resistance to RIF was founded at 2.6% (37) patients. In 44% (633) cases identified multi drug resistance (MDR) strains of the MBT, at the same time resistant to RIF and INH.

Regional distribution of drug resistance strains:

1.Mono resistance to INH: Tashkent region 30.3% (57 out of 188),Tashkent city 17.5%, Samarqand region 9.5%

2.Mono resistance to RIF: Fergana region 24.4% (9 out of37), Tashkent region 16.2%, Namangan region 13.5%

3.MDR strains: Fergana region 20.9% (132 out of 633), Tashkent region 18.3%, Andijan region 17%, Tashkent city 19.3%

Conclusion: Thus, in the structure of drug resistance strains dominated MDR strains (44%). The largest number of cases with mono-resistance to RIF occurred in the Fergana region (24.4%) and mono-resistance to INH in the Tashkent region (30.3%). MDR strains of MBT were more common at Fergana (20.9%) and Andijan (17%) regions. Further inquiry of the problem continues.
The use of influenzal (IV) and pneumococcal (PV) vaccine in patients, staff and visitors at a university hospital in two periods
Authors: Pablo Fescina, Vanina Martin, Fernanda Ramundo, Gustavo Lonegro, Ileana Palma, Carlos M. Luna
Journal: European Respiratory Journal (2011)

Aims:  To determine the trend of IV and PV coverage for the at risk population comparing the years 2001 and 2010.   Methods:  1191 adults (507 in 2001 and 684 in 2010), including patients, relatives, health care workers, medical students and hospital employees, were interviewed at the hospital. They were asked about age, medical history, their knowledge about IV and PV and vaccination history. At risk population was considered according with the current national guidelines.   Results:  Among the people with indications for IV, it was received by 50.1% in 2001 and 63.1% in 2010 (p   The trend of vaccination rate improved significantly for few indications; for IV in health care workers (21.2% vs. 77.7%, p  Analyzing 2001 and 2010 together, IV rate was higher in retired people >65 years old included in a social security program (PAMI) consisting in intensive advertising, free delivery and administration; than in those not included in such program (62.1% vs. 46.4%, p=0.001).   Conclusions:  Vaccination coverage remains low, particularly for PV. Improvement of IV and PV require better awareness, changes in clinical practice, deliver mechanisms and surveillance to assess the progress.
International Collaborative Ovarian Neoplasm Trial 1: A Randomized Trial of Adjuvant Chemotherapy in Women With Early-Stage Ovarian Cancer
Authors: Nicoletta Colombo, David Guthrie, Stefania Chiari, Mahesh Parmar, Wendi Qian, Ann Marie Swart, Valter Torri, Christopher Williams, Andrea Lissoni, Cristina Bonazzi
Journal: JNCI Journal of the National Cancer Institute (2003)

The question of whether platinum-based adjuvant chemotherapy can improve outcomes in patients with early-stage epithelial ovarian cancer is an important one. We carried out a multicenter, open randomized trial to determine whether adjuvant chemotherapy would improve overall survival and prolong recurrence-free survival in women with early-stage epithelial ovarian cancer.Between August 1991 and January 2000, 477 patients in 84 centers in five countries were randomly assigned to receive either adjuvant chemotherapy immediately following surgery (n = 241) or no adjuvant chemotherapy until clinically indicated (n = 236). Kaplan-Meier curves of overall survival and recurrence-free survival were compared using the Mantel-Cox version of the log-rank test. All statistical tests were two-sided.Women who received adjuvant chemotherapy had better overall survival than women who did not (hazard ratio [HR] of 0.66, 95% confidence interval [CI] = 0.45 to 0.97; P =.03). These results translate into 5-year survival figures of 70% for women who did not receive adjuvant chemotherapy and 79% for women who did receive adjuvant chemotherapy, a difference of 9% (95% CI = 1% to 15%). Adjuvant chemotherapy also improved recurrence-free survival (HR = 0.65; 95% CI = 0.46 to 0.91; P =.01). These results translate into 5-year recurrence-free survival figures of 62% for women who did not receive adjuvant chemotherapy and 73% for women who did receive adjuvant chemotherapy, a difference of 11% (95% CI = 3% to 18%).These results suggest that platinum-based adjuvant chemotherapy improves survival and delays recurrence in patients with early-stage ovarian cancer.
Changes in respiratory system reactance (Xrs) during the first lung volume recruitment in preterm lambs on high frequency oscillatory ventilation (HFOV)
Authors: Emanuela Zannin, Miria Natile, David Tingay, Peter Dargaville, Maria Luisa Ventura, Elisabeth Perkins, Risha Bhatia, Paolo Tagliabue, Raffaele Dellacà
Journal: European Respiratory Journal (2012)

The aim of this study was to assess the dynamic changes in respiratory mechanics during the first stepwise increase of mean airway pressure (MAP) in preterm lambs receiving HFOV.  Six 132d preterm lambs were commenced on HFOV at MAP of 14 cmH2O and frequency (fosc) of 10Hz. Five min after birth MAP was increased up to 30 cmH2O in 2-min steps of 4 cmH2O. At the beginning (t0) and at the end (t1) of each step fosc was reduced to measure Xrs at 5Hz. Lung volume (VL) changes were simultaneously measured by electrical impedance tomography.  VL monotonically increased during the recruitment manoeuvre (RM). In average only the 22±2% (mean±SD) of the total change occurring at each step immediately followed the change in MAP, while the remaining 78±2% occurred over the next 2 min. Xrs at first decreased, then it increased over time stabilizing to a higher value compared with the lower MAP step.  During the first RM of an immature lung, VL recruitment is a very-time dependent phenomenon and when MAP is increased, stabilization to a higher lung volume requires few minutes and is preceded by tissue distension. These data suggest that monitoring lung mechanics during the first RM could maximise the efficacy of the procedure minimising mechanical stress to lung tissues.
Impaired urinary ammonium excretion in patients with isolated proximal renal tubular acidosis.
Authors: L G Brenes, M I Sanchez
Journal: Journal of the American Society of Nephrology (1993)

During previous studies in patients with isolated proximal renal tubular acidosis (pRTA), the rates of urinary ammonium excretion were considered inappropriately low for their state of chronic metabolic acidosis. These observations were made while the patients were on a normal diet as well as when they were undergoing a short ammonium chloride test. Because these findings suggested an impaired ability to excrete maximal amounts of ammonium, the response to the 3-day acid loading test was evaluated in eight patients with isolated pRTA and in 10 normal control subjects. Plasma creatinine, acid-base, and electrolyte values were analyzed before and after 3 days of ingesting 2 mmol/kg.24 h of ammonium chloride. Twenty-four-hour urine specimens were collected the day before and on the third day of acid loading to determine urine pH, as well as the rate of excretion of NH4+ and titratable acid in milliequivalents per 24 h per 1.73 m2. During the basal state, all patients with pRTA had hyperchloremic metabolic acidosis and they excreted urine of lower pH (5.51 +/- 0.18 versus 6.00 +/- 0.13; P < 0.05) and greater titratable acid (29.1 +/- 4.3 versus 21.8 +/- 1.4; P < 0.05); however, they had rates of NH4+ excretion similar to those of controls. On the third day of acid loading, they excreted urine of lower pH (4.66 +/- 0.03 versus 5.00 +/- 0.03; P < 0.05) and equivalent amounts of titratable acid, whereas their NH4+ excretion was significantly less than that of controls (47.7 +/- 4.4 versus 76.3 +/- 5.7; P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
REGRESSION NEUROSES AND SCHIZOPHRENIA
Authors: ANNETTE C. WASHBURNE, EDWARD R. HODGSON
Journal: American Journal of Psychiatry (1941)

1. An attempt has been made to contrast the symptoms and signs observed in 10 cases of schizophrenia and in 30 cases of regression neuroses. 2. All cases occurred in university students. 3. The impressions resulting from a statistical study would indicate that the following symptoms and signs occurred twice as frequently in the schizophrenics as in the regression neuroses: (a) rigid personality, (b) extreme deficiency in good social attitudes, (c) narrow interests, (d) poor design for living, (e) tendency for suicidal ideas, (f) unsatisfactory school work, and (g) lack of insight. 4. While no conclusions are attempted it is suggested that combinations of 3 or more of the above symptoms and signs might be regarded as suggesting a schizophrenic reaction. 5. With these symptoms and signs in mind a further study is being undertaken in order to test their possible value in differential diagnosis between schizophrenia and regression neuroses.
Docetaxel and cisplatin combination chemotherapy for advanced epithelial ovarian cancer with bulky residual disease
Authors: A. Shaharyar, K. Shabbir, M. Hafeez, Z. Alauddin, E. U. Rehman
Journal: Journal of Clinical Oncology (2006)

15030 Background: The combination of docetaxel and cisplatin as an alternative to the gold standard carboplatin and paclitaxel chemotherapy has not been explored in our patients. Docetaxel is more potent of the taxanes, therefore, this combination might yield a better outcome. This phase II study was designed to evaluate the efficacy and toxicity of docetaxel and cisplatin combination in epithelial ovarian cancer with bulky residual disease. Methods: Thirty-two new patients were enrolled between November 2003 and August 2005. Eligible patients had histopatholgically confirmed epithelial ovarian cancer, were older than 18 years and had FIGO stage IIC-IV cancer with bulky residual disease after primary cytoreductive surgery. Patients had a KPS &gt;70 with adequate marrow and hepatic function. Patients with creatinine clearance by Cockroft-Gault formula of &gt;60 ml/min were included. Written informed consent was obtained. Patients with diabetes mellitus, peripheral neuropathy, or cardiac co morbidity were excluded. Docetaxel and cisplatin were given at a dose of 75 mg/m 2 each on day-1 of a 21-day cycle. Dexamethasone 8 mg was given thrice before and thrice after and tropisetron 5mg was given one hour before and 12 hours after chemotherapy. Docetaxel was given in 250 ml of NaCl in one-hour followed by cisplatin 75 mg/m 2 in 1L of NaCl in 3 hours with pre and post hydration. NCI toxicity criteria version 2.0 and RECIST was used for evaluation. Results: Thirty patients were evaluable for response and toxicity. Final evaluation revealed CR in 12 (40%) (95% CI, 22.7–59.4%), PR in 14 (46.6%) with an ORR of 86.6% (95% CI, 69.3–96.2%). Three (10%) had SD and 1 (3.33) had PD. Grade 2 toxicity included alopecia 18 (60%), vomiting 6 (20%), diarrhea 7 (23.3%) and stomatitis in 5 (16%). Grade 3 and 4 neutropenia were seen in 12 (40%) and 9 (30%) respectively. Sensory neuropathy of grade 1 and 2 was seen in 4 (13.3%) and 2 (6.7%) respectively. Conclusion: Docetaxel and cisplatin combination chemotherapy is an effective and safe regimen in epithelial ovarian cancer with bulky residual disease. It gives a high overall response rate and has a manageable toxicity profile. No significant financial relationships to disclose.
Combined endoscopic evaluation of central lung cancer spread using autofluorescence and spectroscopy
Authors: Yulia Kulakova, Andrey Arseniev, Evgeny Levchenko, Anton Barchuk, Alexey Barchuk, Andrey Akopov
Journal: European Respiratory Journal (2011)

Objective:  To estimate the diagnostic value of autofluorescence bronchoscopy with spectroscopy in determination of lung cancer endobronchial spread.   Material and methods:  The study included 78 patients with central NSCLC stage II-IV. Combined endoscopic investigation included: bronchoscopy in conventional mode (CB), spectroscopy in conventional mode (CS), bronchoscopy in autofluorescence mode (AFB) and spectroscopy in autofluorescence mode (AFS). Integrated system for autofluorescence and spectroscopy was used. The data obtained were compared with the results of histological study of biopsy samples from the respective sites.   Results:  The sensitivity and specificity of the combination of AFB and AFS was 97.1% and 88.3%, respectively vs. CB and CS - 66,7% and 86,9%, respectively. Maximal diagnostic value had green-red ratio (GRR) - the ratio of intensity in the green range (500-565 nm) to the red range (620-760 nm). For normal tissue mean GRR was 3,4±0,9, on the borders of tumor growth in 97% of the cases did not exceed 2.0 (mean 1,2±0,4) (p = 0.02), over areas of tumor tissue – in all cases less than 1.0 with an average of 0,7±0,2 (p = 0,001). In 97,1% of cases, the data AFB and AFS is fully consistent with the results of histological studies (p = 0,02). In general, in 30,4% cases AFB and AFS more accurately clarified the extent of tumor in comparison with CB and CS.   Conclusions:  Combination of AFB and AFS helps to objectively and accurately establish the boundaries of the tumor spread in bronchus/trachea.
Cardiorespiratory effects of immunotherapy with interleukin-2.
Authors: R E Lee, M T Lotze, J M Skibber, E Tucker, R O Bonow, F P Ognibene, J A Carrasquillo, J H Shelhamer, J E Parrillo, S A Rosenberg
Journal: Journal of Clinical Oncology (1989)

The administration of interleukin 2 (IL-2) and lymphokine-activated killer (LAK) cells can mediate the regression of cancer. Treatment with IL-2 is associated with significant cardiorespiratory effects, as well as a leaky capillary syndrome requiring careful fluid management. A mild reversible depression of cardiac function is also associated with IL-2 treatment. All patients treated with recombinant IL-2 alone, with transfer of LAK cells, or with cyclophosphamide between December 1984 and September 1987 (total of 423 treatment courses in 317 total patients) were evaluated as to the development of significant cardiorespiratory toxicity. Of the 423 treatment courses, only 1.8% were associated with severe peripheral edema and only 2.8% and 3.1% respectively, were associated with significant ascites or pleural effusions. Thirty-nine of 423 patients (9.2%) had severe respiratory distress and 27 patients required intubation (6.4%). Cardiovascular effects included tachycardia and hypotension requiring vasopressor administration in 65% and intravenous (IV) fluid administration. Weight gain greater than or equal to 10% of body weight was noted in 32% of the 423 patients. Arrhythmias were primarily supraventricular (9.7%) and responded well to conventional medical treatments. Angina or ischemic changes were noted in 2.6% of patients and myocardial infarction in 1.2%. IL-2 caused peripheral vasodilation, with a significant decrease in peripheral vascular resistance (2,254 +/- 398 v 1,303 +/- 351 dyne.s.cm-5, P less than .0001), and an increase in heart rate (66.2 +/- 10 v 104.3 +/- 9.6 beats/min, P less than .0001). There was also evidence of mild cardiac dysfunction, with a significant decrease in the left ventricular stroke work (LVSW) index (P less than .0001) and ejection fraction (LVEF) (from 58% +/- 10% to 52% +/- 9%, P less than .03). A repeat LVEF performed after 1 to 3 months, had returned to baseline values (60% +/- 10%). A mean 64% increase in the rate of disappearance of radioactive iodine (125I) albumin (P less than .05) consistent with the development of a leaky capillary syndrome was noted. Patients with underlying cardiorespiratory diseases may be at greater risk during IL-2 administration and should not be selected to undergo this treatment.
Airways Involvement in Rheumatoid Arthritis
Authors: THIERRY PEREZ, MARTINE REMY-JARDIN, BERNARD CORTET
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

The aim of the present study was to assess the prevalence and characteristics of airways involvement in rheumatoid arthritis (RA) patients in the absence of interstitial lung disease. We prospectively evaluated, with high-resolution computed tomography (HRCT) and pulmonary function tests (PFTs), 50 patients with RA (nine males and 41 females; mean age: 57.8 yr), including 39 nonsmokers and 11 smokers (mean cigarette consumption: 15.3 pack-yr) without radiographic evidence of RA-related lung changes. PFTs demonstrated airway obstruction (i.e., reduced FEV1/VC) in nine patients (18%) and small airways disease (SAD) (i.e., decreased FEF(25-75), defined as exceeding the predicted value by 1.64 residual SD [RSD] or more, and/or an increased phase III slope > 2 SD by single breath nitrogen washout) in four patients (8%). HRCT demonstrated bronchial and/or lung abnormalities in 35 cases (70%), consisting of air trapping (n = 16; 32%), cylindral bronchiectasis (n = 15; 30%), mild heterogeneity in lung attenuation (n = 10; 20%), and/or centrilobular areas of high attenuation (n = 3; 6%). Airway obstruction and SAD were correlated with the presence of bronchiectasis and bronchial-wall thickening (p = 0.003), and with bronchial infection (p = 0.01), but were unrelated to rheumatologic data. FEF(25-75) was reduced and the slope of phase III was increased in patients with airway changes on HRCT scans, whereas no PFT abnormalities were found in 13 of 15 patients with normal HRCT scans. HRCT depicted features of SAD in 20 of the 33 patients with normal PFTs. HRCT findings were unrelated to rheumatologic data. A high prevalence of airway abnormalities as assessed with HRCT and/or PFTs was observed in our RA population. HRCT appears to be more sensitive than PFTs for detecting small airways disease.
Invasive pulmonary aspergillosis in adult acute leukemia: clinical clues to its diagnosis.
Authors: S L Gerson, G H Talbot, E Lusk, S Hurwitz, B L Strom, P A Cassileth
Journal: Journal of Clinical Oncology (1985)

Invasive pulmonary aspergillosis, a leading cause of morbidity and mortality in patients with acute leukemia, is difficult to diagnose antemortem because its signs and symptoms are ill-defined. To refine the clinical description of this infection, we reviewed our experience with 15 pathologically documented cases of invasive pulmonary aspergillosis in a population of 60 patients treated for acute leukemia. Findings occurring significantly more often (P less than or equal to .001) among cases than controls included pleuritic chest pain; acute sinus tenderness, and nasal discharge, epistaxis and eschar; rales; development of multilobar infiltrates after the 14th hospital day; and presence of nodular or cavitary infiltrates. In addition, patients with invasive pulmonary aspergillosis had a significantly prolonged duration of granulocytopenia, more febrile days and febrile episodes without a fever diagnosis and more febrile days on antibiotics (P less than or equal to .001 in all). This complex of findings should improve the clinician's ability to diagnose invasive pulmonary aspergillosis in patients with acute leukemia.