tbuckley/cabot-search huggingface dataset:
Prediction of long-term survival by flow cytometric analysis of cellular DNA content in patients with advanced ovarian cancer.
Authors: M L Friedlander, D W Hedley, C Swanson, P Russell
Journal: Journal of Clinical Oncology (1988)

The prognostic value of cellular DNA content in ovarian cancer (malignant common epithelial tumors) was investigated by flow cytometric analysis of paraffin-embedded tumor blocks from 128 previously untreated patients with International Federation of Gynecology and Obstetrics (FIGO) stage III and IV ovarian cancer entered in a prospective clinical trial of combination v sequential therapy with chlorambucil and cisplatin. Seventy-three percent of tumors were aneuploid and 27% were diploid. Multivariate analysis using a Cox model showed that cellular DNA content (P less than .001) and FIGO stage (P less than .02) were the only significant independent prognostic variables. The median survival was 13 months for patients with aneuploid tumors and 60 months for patients with diploid tumors (P less than .0001). Further analysis indicated that the good prognosis associated with diploid tumors was limited to patients with stage III disease, all patients with stage IV (spread beyond the peritoneal cavity or liver metastases) disease having a poor prognosis irrespective of ploidy. On pathological review, nine borderline ovarian tumors (of low malignant potential) were identified, and seven of these were diploid. These tumors have an unusually favorable prognosis, despite apparent dissemination within the peritoneal cavity, a paradox which is often difficult to explain using conventional histological criteria. Although the vast majority of tumors in this study (93%) were classified as invasive epithelial ovarian cancers, it is possible that some of the patients with stage III diploid tumors may have had malignancies that were predominantly of low malignant potential, thus accounting in part for the prognostic significance of DNA content. By incorporating flow cytometric DNA analysis with careful histopathological assessment, it may be possible to better identify patients with an inherently good prognosis. This assumes particular importance, as the relatively favorable prognosis of patients with stage III diploid ovarian tumors appears to be independent of the type of treatment.
PEEP titration with lung ultrasound and electrical impedance tomography in an ARDS animal model
Authors: Elena Prina, Eduardo Leite Vieira Costa, Otávio Tavares Ranzani, Susimeire Gomes, Roberta Ribeiro De Santis Santiago, Myiuki Nakamura, Marcelo Britto Passos Amato, Antoni Torres, Carlos Roberto Ribeiro de Carvalho
Journal: European Respiratory Journal (2014)

Background: In ARDS, the identification of PEEP that confers the best compromise between lung collapse and hyperdistension remains a challenge. Electrical impedance tomography (EIT) quantifies recruitable collapse and hyperdistension. Lung ultrasound (LUS) detects PEEP-induced recruitment.  Aims:  to compare the collapse estimated with EIT and LUS during PEEP titration in an ARDS animal model; to compare the PEEP chosen based on EIT (PEEP EIT ) and on LUS (PEEP US ). Methods:  we evaluated 7 mechanically ventilated pigs with ARDS induced by saline-lavage and injurious ventilation. After recruitment, we titrated the PEEP while collecting data with EIT and performing LUS of the worst lung area. We defined a LUS score: 0-normal, 1-separated B lines, 2-confluent B lines, 3-subpleural consolidation, 4-partial and 5-extensive consolidation. PEEP EIT  was defined as the lowest PEEP with EIT collapse≤1% and PEEP US  as the lowest PEEP with LUS scorel4. Results:  LUS patterns 4/5 had 100% sensitivity, 65% specificity to detect EIT collapseg1%(fig a). In two animals, LUS detected fixed collapse, which cannot be detected by EIT. PEEP US  was highly correlated with PEEP EIT , although higher (fig b,c) and with a trend to more hyperdistension (31±16% vs 19±8 p=0.15)   Conclusions:  LUS patterns had a good correlation with collapse estimated by EIT.The methods seem to be complementary since LUS detected fixed collapse, while EIT detected hyperdistension.
Treatment of malignant germ cell tumors of the ovary with bleomycin, etoposide, and cisplatin.
Authors: D M Gershenson, M Morris, A Cangir, J J Kavanagh, C A Stringer, C L Edwards, E G Silva, J T Wharton
Journal: Journal of Clinical Oncology (1990)

Since 1984, we have treated 26 patients with malignant ovarian germ cell tumors with a combination of bleomycin, etoposide (VP-16), and cisplatin (BEP) at The University of Texas MD Anderson Cancer Center (UTMDACC). The median age of the patients was 19 years (range, 8 to 32). All patients underwent initial surgery (unilateral salpingo-oophorectomy in 14, unilateral salpingo-oophorectomy plus abdominal hysterectomy in one, and bilateral salpingo-oophorectomy with or without hysterectomy in 11 patients). Twenty patients had no residual disease, three had less than or equal to 2 cm (one each, dysgerminoma, mixed, and immature teratoma), and three had more than 2 cm lesions (two dysgerminomas, one endodermal sinus tumor). Fourteen patients had pure dysgerminoma (five, stage I; one, stage II; six, stage III; and two, recurrent), and 12 had nondysgerminomatous tumors (five, stage I; two, stage II; three, stage III; and two, recurrent). All four patients with clinically measurable disease had a complete response. All four patients who underwent second-look laparotomy had negative findings. Twenty-five patients (96%) remain in sustained remission 10.4 to 54.4 months from the start of chemotherapy. One patient died of progressive disease 14 months after beginning chemotherapy. We conclude that the BEP regimen has excellent activity and acceptable toxicity in patients with malignant ovarian germ cell tumors.
Keap1–Nrf2 Interaction Suppresses Cell Motility in Lung Adenocarcinomas by Targeting the S100P Protein
Authors: Ming-Hsien Chien, Wei-Jiunn Lee, Feng-Koo Hsieh, Chia-Feng Li, Tsu-Yao Cheng, Ming-Yang Wang, Jin-Shing Chen, Jyh-Ming Chow, Yi-Hua Jan, Michael Hsiao, Kuo-Tai Hua, Min-Liang Kuo
Journal: Clinical Cancer Research (2015)

Kelch-like ECH-associated protein 1 (Keap1) is an E3 ligase participated in the cellular defense response against oxidative stress through nuclear factor erythroid-2-related factor 2 (Nrf2). However, the role of Keap1 in regulating cancer motility is still controversial. We investigated the contribution of the Keap1-Nrf2 axis in the progression of non-small cell lung cancer (NSCLC).The expression of Keap1 and Nrf2 was examined via immunohistochemistry, real-time PCR, and Western blot analysis in a cohort of NSCLC tissues and cells. A series of in vivo and in vitro assays was performed to elucidate the contribution of the Keap1-Nrf2 axis in lung cancer mobility and progression.Keap1 expression was decreased in specimens from NSCLC patients with lymph node metastasis compared with patients without metastasis. Higher Keap1 expression levels were correlated with the survival of NSCLC patients. Moreover, manipulation of Keap1 expression affected cell migration/invasion abilities. Depletion of Nrf2 relieved the migration promotion imposed by Keap1 suppression. Mechanistic investigations found that S100P was downregulated in both Keap1-overexpressing and Nrf2-knockdown NSCLC cells. Overexpression of Keap1 and knockdown of Nrf2 both suppressed S100P expression in NSCLC cells. Knockdown of S100P inhibited cell migration in highly invasive NSCLC cells and also relieved the migration promotion imposed by Keap1 suppression in weakly invasive NSCLC cells.Our findings suggest that Keap1 functions as a suppressor of tumor metastasis by targeting the Nrf2/S100P pathway in NSCLC cells. In addition, overexpression of Keap1 may be a novel NSCLC treatment strategy and/or useful biomarker for predicting NSCLC progression.
Increased within-test variability may bias estimates of the LCI
Authors: Sanja Stanojevic, Renee Jensen, Padmaja Subarrao, Felix Ratjen
Journal: European Respiratory Journal (2013)

Background: The Multiple Breath Washout (MBW) test has been shown to be an important research tool and has the potential for wider use in clinical practice. Feasibility for pediatric clinical settings may be improved if the testing time can be shortened.We investigated whether it is possible to minimize the number of trials performed, without affecting the precision of the test.  Method: 42 healthy and 37 children with CF performed nitrogen MBW (Exhalyzer D, Eco Medics AG, Switzerland). The mean LCI and coefficient of variation (CV) were calculated from all technically acceptable trials (i.e. no obvious leaks, end of test criteria met, etc., with some adaptations for children). In addition, the first acceptable trial, and the best trial (defined as the first acceptable trial with a breathing pattern most reflective of quiet tidal breathing) were selected. The mean LCI was compared to the LCI of the first, as well as the best trial.  Results: As the CV increased, the magnitude of the difference between the mean LCI and first LCI also increased. Compared to the best LCI, the mean LCI was higher in 70% of subjects. The difference between the best LCI and mean LCI also increased as the CV increased. Using the best LCI as a benchmark, 70% of subjects had a reproducible LCI within 5% and 97% within 10%.  Conclusions: These findings suggest that the average LCI from several MBW trials can over-estimate LCI, especially if the variability between trials is high. Reporting the LCI from the best trial, which reflects an ideal quiet tidal breathing pattern, may minimize testing time and improve the accuracy of the test without affecting precision. In addition the CV may be a useful quality control measure.
Mycobacterial load affects adenosine deaminase 2 levels of tuberculous pleural effusion
Authors: Chang Ho Kim, Jaehee Lee, Jisook Lee, Jacqueline M Cliff, Frederic Toulza, Steven Smith, Seung Soo Yoo, Shin Yup Lee, Seung Ick Cha, Jae Yong Park, Hazel M Dockrell
Journal: Journal of Infection (2015)
Late-breaking abstract: The certification of allergy-, asthma- and COPD-clinics in primary care in Southern Sweden
Authors: Birgitta Lagorstrand, Leif Bjermer, Magnus Kåregård, Alf Tunsäter, Kerstin Romberg
Journal: European Respiratory Journal (2014)

In primary health care asthma, allergies and COPD are common diseases with increasing prevalence, causing both  human suffering and huge costs for society. A structured treatment with well-functioning asthma/COPD-clinics  has been found to improve the care of these patients.  In 2013 the County Council/Region Skane made a decision to certify the asthma/COPD-clinics in primary health care.  Swedish national criteria for asthma/COPD clinics from 2008 were used.(1)   aim of the certification process was to ensure the quality of care regarding the patients with asthma, allergy and COPD.  Methods; A web-based questionnaire was sent all 150 primary care clinics in Skane and 108 clinics responded.  Requirements that must be met for before certification  1. An educated asthma/COPD nurse 15 credits (Bolonga) or more  2. Dedicated time for the nurse should be at least 2 hours a week per 1,000 listed patients  2. A specialist in general medicine should be medically responsible for the clinic.  3. Both the nurse and the general practitioner must have completed the  Spirometry driving license (a Swedish national education program in spirometry).  4. Smoking cessation program  6. Registration in  Swedish Airway Registry.  Results In January 2014, only ten of the 150 clinics qualified, but already after four months the criteria were fulfilled by 48 clinics.  level of education has increased, more members of the staff have been trained  in spirometry, the dedicated patient time for the nurse has been extended and more clinics have connected to The  Swedish airway registry.  Conclusion  By certifying asthma and COPD clinics both the education level and the allocated time for patients can be  increased.
Variation in heat-shock proteins among species of desert fishes (Poeciliidae, Poeciliopsis).
Authors: C N White, L E Hightower, R J Schultz
Journal: Molecular Biology and Evolution (1994)

Analysis of the heat-shock proteins (hsps) of six closely related species of Poeciliopsis demonstrated the existence of biochemical diversity in the hsp100, hsp70, hsp60, and hsp30 protein families among species. Each species expressed five to seven hsp70-related isoforms. Constitutive 70-kD isoforms were identical among species, but four different patterns of heat-inducible isoforms were seen in these six species. Members of the hsp70 family of molecular chaperones are included among the most highly conserved proteins known, and the possibility of variation in hsp70 among closely related species has rarely been addressed. The hsp30 family is known to be less conserved than the hsp70 family, and, as expected, the Poeciliopsis hsp30 patterns showed more variation. Most of the hsp30 isoforms characteristic of a particular species were unique to that species. Hsp100 and hsp60 were identical in five of the species, but alternate isoforms were found in P. monacha. The small size and limited geographical distribution of the P. monacha population have probably contributed to the uniqueness of the monacha pattern. Two of the species were shown to acquire thermotolerance, the ability to withstand normally lethal temperatures when subjected to a gradual temperature increase. Rapid-heating protocols commonly used to establish critical thermal maxima of organisms do not include this inducible component of thermoresistance and therefore do not adequately assess an organism's capacity to withstand thermal stress.
Prevention of glomerular dysfunction in diabetic rats by treatment with d-alpha-tocopherol.
Authors: D Koya, I K Lee, H Ishii, H Kanoh, G L King
Journal: Journal of the American Society of Nephrology (1997)

Because d-alpha-tocopherol (vitamin E) has been shown to decrease diacylglycerol (DAG) levels and prevent the activation of protein kinase C (PKC), which is associated with retinal and renal dysfunctions in diabetes, the study presented here characterized the effect of d-alpha-tocopherol treatment to prevent glomerular hyperfiltration and increased albuminuria as well as PKC activities in streptozotocin (STZ)-induced diabetic rats. Two weeks after the induction of diabetes, total DAG content and PKC activity in glomeruli were significantly increased in diabetic rats by 106.4 +/- 16.8% and 66.4 +/- 8.4%, respectively, compared with control rats. Intraperitoneal injection of d-alpha-tocopherol (40 mg/kg of body weight) every other day prevented the increases in total DAG content and PKC activity in glomeruli of diabetic rats. Glomerular filtration rate (GFR) and filtration fraction (FF) were significantly elevated to 4.98 +/- 0.34 mL/min and 0.36 +/- 0.05, respectively, in diabetic rats, compared with 2.90 +/- 0.14 mL/min and 0.25 +/- 0.02, respectively, in control rats. These hemodynamic abnormalities in diabetic rats were normalized to 2.98 +/- 0.09 mL/min and 0.24 +/- 0.01, respectively, by d-alpha-tocopherol. Albuminuria in 10-wk diabetic rats was significantly increased to 9.1 +/- 2.2 mg/day compared with 1.2 +/- 0.3 mg/day in control rats, whereas d-alpha-tocopherol treatment improved albumin excretion rate to 2.4 +/- 0.6 mg/day in diabetic rats. To clarify the mechanism of d-alpha-tocopherol's effect on DAG-PKC pathway, the activity and protein levels of DAG kinase alpha and gamma, which metabolize DAG to phosphatidic acid, were examined. Treatment with d-alpha-tocopherol increased DAG kinase activity in the glomeruli of both control and diabetic rats, by 22.6 +/- 3.6% and 28.5 +/- 2.3% respectively, although no differences were observed in the basal DAG kinase activity between control and diabetic rats. Because immunoblotting studies did not exhibit any difference in the protein levels of DAG kinase alpha and gamma, the effect of d-alpha-tocopherol is probably modulating the enzyme kinetics of DAG kinase. These findings suggest that the increases in DAG-PKC pathway play an important role for the development of glomerular hyperfiltration and increased albuminuria in diabetes and that d-alpha-tocopherol treatment could be preventing early changes of diabetic renal dysfunctions by normalizing the increases in DAG and PKC levels in glomerular cells.
A new proposal for OSA classification in children based on cardiovascular outcome
Authors: Silke A.T. Weber, Victor dos Santos, José Maurício Lopes Neto, Luiz Cuadrado Martins
Journal: European Respiratory Journal (2012)

Introduction: Pediatric OSA is associated to cardiovascular repercussions (CVR), adenotonsillectomy(AT) is considered its treatment of choice. We hypothesized that OSA leads to early CVR as loosing of nocturnal blood pressure dipping (NBPD); OSA treatment (AT) will recover NBPD.

Aim: to analyse which polysomnographic(PSG) criteria best defines OSA in children, based on the absence of NBPD before and its recovering after AT.

Methods: We included children with regular snoring, observed respiratory pauses and hypertrophy of the tonsills. Children with persisting snoring after AT,diagnosis of cardiovascular, renal or neurologic disease and obesity were excluded. Children realized PSG and 24-hour blood pressure monitoring before and six months after AT. AI and AHI were calculated, the presence or absence of NBPD was described before and after AT. Three current PSG definitions for OSA (D1:AHI>1; D2:AI>1 & AHI>4; D3: AHI>5) were tested for the best correlations of OSA and CVR before and NBPD recovering after AT(McNemar, Odd's ratio).

Results: 26 children, 8-12 years old, were included. AHI varied from 0,0 to 23,2. 10 children presented loosing of NBPD before, 4 persisted after AT. For D1 (AHI>1) OSA diagnosis showed no significant association to CVR neither before, nor after AT. For D3 (AHI>5) OSA diagnosis showed a significant correlation to CVR before AT, but not after surgery. For D2 (AI>1 & AHI>4) OSA diagnosis showed significant correlation to CVR before and after surgery.

Conclusion: Considering NBPD and surgery outcome, we identified AI>1 & AHI>4 as the best definition for OSA in children. Larger studies focusing CVR and surgical outcome should be realized to better define PSG criteria and OSA.
Guest Editorial: Fertilizers, Water Quality, and Human Health
Authors: Robert E. Criss, M. Lee Davisson
Journal: Environmental Health Perspectives (2004)

Fertilizer use has increased 10-fold since World War II. Current application rates are staggering and greatly exceed the amounts absorbed by plants. For example, the average amount of nitrogen applied to corn in the Midwest is approximately 160 kg/hectare/year, and in California > 200 kg/hectare/year is added to more than 3 million cultivated hectares [U.S. Department of Agriculture (USDA) 1991, 2003].

The geochemical fate of this excess nitrate is complex, but it is evident that much of it becomes non–point source pollution that degrades both surface waters and valuable groundwater supplies. Large increases in nitrate loads accompany flood pulses in midwestern rivers, and these loads clearly originate in the “Corn Belt,” where nitrate application is highest (Goolsby et al. 1993; Meade 1995; Winston and Criss 2003). Much of this load ends up in the Gulf of Mexico, where a hypoxic “dead zone” of up to 20,000 km2 develops each year, much to the detriment of the aqueous environment (e.g., Goolsby 2000; McIsaac et al. 2001).

Other paths convey nitrate downward into shallow groundwater, an essential resource that provides the domestic water supply for nearly 50% of Americans. Nitrate contamination of well water is now widespread in the United States (Nolan et al. 1998). Numerous case histories document that the change from potable to nonpotable nitrate contents can occur very rapidly (e.g., Snow et al. 1988). Moreover, well contamination is aggravated by low groundwater levels (Davisson and Criss 1993), so one can predict that further rapid degradation of drinking-water supplies will accompany the current drought conditions in the western United States. This problem has been most severe in California, where several municipalities in the Central Valley and coastal valleys such as the Salinas have been forced to abandon entire well fields because nitrate levels have risen sharply above the maximum contaminant level (Davisson and Criss 1996).

These contaminant levels were established to prevent acute exposure that leads to methemoglobinemia, or “blue baby syndrome,” in infants, which can be potentially fatal (Knobeloch et al. 2000). Further, chronic exposure to nitrate-contaminated drinking water in Spain, China, and Taiwan has more recently been linked to increased risk of gastric cancer (Knobeloch et al. 2000; Morales-Suarez-Varela et al. 1995; Xu et al. 1992; Yang et al. 1998), which may have profound implications for potential health risks from our widespread non–point source nitrate contamination in the United States.

Widespread nitrate contamination is not necessary. Nitrate contamination is one of many problems that can arise when profits are based on short-term economics, in this case on maximized crop yields. Such faulty cost analysis neglects the long-term consequences of commercial activities and the fact that those consequences need not be confined to the properties where problems originate. We can do better.
Lung Cancer Mortality in Workers Exposed to Sulfuric Acid Mist and Other Acid Mists
Authors: J J Beaumont, J Leveton, K Knox, T Bloom, T McQuiston, M Young, R Goldsmith, N K Steenland, D P Brown, W E Halperin
Journal: JNCI Journal of the National Cancer Institute (1987)

Mortality patterns were studied in 1,165 workers exposed to sulfuric acid mist and other acid mists (primarily hydrochloric acid mist) in steel-pickling operations. Standardized mortality ratio (SMR) analysis of the full “any acid exposure” cohort (n = 1,165), with the use of U.S. death rates as a standard, showed that lung cancer was significantly elevated, with a mortality ratio of 1.64 [95% confidence interval (CI) = 1.14–2.28, based on 35 observed deaths]. The lung cancer mortality ratio for workers exposed only to sulfuric acid (n=722) was lower (SMR = 1.39), but further restriction to the time 20 years and more from first employment in a job with probable daily sulfuric acid exposure (≈0.2 mg/m3) yielded a mortality ratio of 1.93 (95% CI = 1.10–3.13). An excess lung cancer risk was also seen in workers exposed to acids other than sulfuric acid (SMR=2.24; 95% CI = 1.02–2.46). When comparison was made to other steel workers (rather than to the U.S. general population) to control for socioeconomic and life-style factors such as smoking, the largest lung cancer excess was again seen in workers exposed to acids other than sulfuric acid (SMR = 2.00; 95% CI = 1.06–3.78). Adjustment for potential differences in smoking habits showed that increased smoking was unlikely to have entirely explained the increased risk. Mortality from causes of death other than lung cancer was unremarkable, with the exception of significantly low rates for deaths due to digestive system diseases.