tbuckley/cabot-search huggingface dataset:
Atrial natriuretic peptide and urinary cyclic guanosine monophosphate in patients with chronic heart failure.
Authors: W T Abraham, J Hensen, J K Kim, J Dürr, E J Lesnefsky, B M Groves, R W Schrier
Journal: Journal of the American Society of Nephrology (1992)

Circulating concentrations of human atrial natriuretic peptide (hANP) are elevated in patients with heart failure; however, the natriuretic effect of hANP is blunted in these patients. In this study, the relationship between urinary cGMP, the second messenger for the natriuretic effect of hANP in vivo, and endogenous hANP was examined in six patients with heart failure and four normal subjects. In addition, right heart catheterization for the determination of central hemodynamics was performed in the heart failure patients. The heart failure patients were in New York Heart Association Classes II to IV and were receiving no medications at the time of the study. Supine plasma hANP and urinary cGMP concentrations were determined on two occasions in each subject, as were right and left atrial pressures in the heart failure patients. At the time of study, the patients were in positive sodium balance, and control subjects were in normal sodium balance. Plasma hANP and urinary cGMP excretion rates were elevated in heart failure patients as compared with those in controls: hANP, 139.0 +/- 42.0 versus 22.0 +/- 6.1 pg/mL (P less than 0.05); urinary cGMP, 1.14 +/- 0.31 versus 0.35 +/- 0.05 nmol/min (P less than 0.05). In heart failure patients, right atrial pressure correlated positively with plasma hANP (r = 0.96; P less than 0.01) and urinary cGMP concentrations (r = 0.93; P less than 0.05) and the excretion rate (r = 0.92; P less than 0.05). Moreover, plasma hANP was strongly correlated with urinary cGMP concentration (r = 0.91; P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Intravenous vinorelbine as first-line and second-line therapy in advanced breast cancer.
Authors: B L Weber, C Vogel, S Jones, H Harvey, L Hutchins, J Bigley, J Hohneker
Journal: Journal of Clinical Oncology (1995)

PURPOSE We evaluated single-agent intravenous (IV) vinorelbine as first- and second-line treatment for advanced breast cancer (ABC) in patients who were not resistant to anthracyclines. Objective tumor response (TR) and toxicity were assessed. PATIENTS AND METHODS A total of 107 women were enrolled onto this multicenter, nonrandomized, open-label phase II study. Patients were stratified into first- and second-line treatment groups, based on prior treatment history. Vinorelbine was initially given at 30 mg/m2/wk, with dose modification for toxicity as indicated. Therapy was continued until disease progression or severe toxicity mandated withdrawal or until the patient asked to be removed from the study. RESULTS The objective response rate for all patients was 34% (95% confidence interval [CI], 25% to 44%): 35% (95% CI, 23% to 48%) for first-line patients and 32% (95% CI, 20% to 47%) for second-line patients. Nine first-line and three second-line patients obtained a complete response (CR). The median duration of objective response was 34 weeks in both groups. The overall survival durations of first- and second-line patients were 67 weeks and 62 weeks, respectively. Granulocytopenia was the predominant dose-limiting toxicity. Two patients died on study as a result of granulocytopenic sepsis. CONCLUSION Single-agent vinorelbine is an effective and well-tolerated agent for first- and second-line therapy of ABC. The results of this study confirm the findings of similar international trials and suggest vinorelbine should be considered a valid treatment option for patients with ABC and a potential component in future combination regimens for this disease.
A Novel Anti-Apoptosis Gene: Re-expression of Survivin Messenger RNA as a Prognosis Marker in Non–Small-Cell Lung Cancers
Authors: Mariano Monzó, Rafael Rosell, Enriqueta Felip, Julio Astudillo, José Javier Sánchez, José Maestre, Cristina Martín, Albert Font, Agustí Barnadas, Albert Abad
Journal: Journal of Clinical Oncology (1999)

The survivin gene is a novel apoptosis inhibitor, related to the baculovirus gene, which is believed to play a pivotal role in fetal development and in cancer. We hypothesised that survivin would be expressed in tumors of patients with non-small-cell lung cancer (NSCLC), and we attempted to determine the influence of survivin re-expression on clinical outcome in patients with up to stage IIIA NSCLC who had undergone radical surgery.We designed a reverse transcriptase polymerase chain reaction (RT-PCR) assay to study the expression of the survivin gene in 83 NSCLC tumor samples and compared the results with relevant clinical and pathologic data.The RT-PCR identified survivin gene transcript in 71 (85. 5%) of the tumor samples and in only 10 (12%) of the paired, histopathologically normal lung samples. There was no relationship between histologic subtype (squamous v nonsquamous) and survivin gene expression. The 12 patients without survivin expression had significantly better overall survival than the 71 patients with survivin expression (P =.01 by univariate analysis; relative risk, 2. 1). There was no significant correlation between survivin expression and age, sex, cigarette smoking, histologic subtype, tumor differentiation, tumor size, or the presence of mediastinal lymph node metastases in surgical specimens.The survivin gene was expressed in a vast majority of NSCLC tumors. We conclude that survivin transcript is a defining diagnostic marker for NSCLC that may also yield prognostic information and, as an apoptosis inhibitor, be an important target in cancer therapy.
Nasal steroids in snorers can decrease snoring frequency – A randomized placebo-controlled crossover trial
Authors: Ioannis Koutsourelakis, Kallirroi Lamprou, Eleni Perraki, Emmanouil Vagiakis, Spyros Zakynthinos
Journal: European Respiratory Journal (2014)

Although it is anecdotally known that nasal obstruction is associated with snoring, it remains unknown whether the application of nasal steroids could decrease oral/oro-nasal breathing and subsequently decrease snoring indices. This study evaluated the effect of nasal budesonide on breathing route pattern and snoring.  Twenty-four snorers were enrolled in a randomized, double-blind, crossover trial of one-week treatment with nasal budesonide compared with one-week treatment with nasal placebo. At the start and end of each treatment, patients underwent nasal resistance measurement and overnight polysomnography (measurement of breathing route pattern and snoring).  Twelve patients were randomly assigned to a one-week treatment with nasal budesonide, followed by two-week washout period and a one-week treatment with the nasal placebo, and 12 patients were randomly assigned to the opposite sequence of treatments. Nasal budesonide was associated with decrease in oral/oro-nasal breathing epochs, decrease of snoring frequency by 15.8% (11.2%-18.8%), and an increase of REM sleep; snoring intensity decreased only in patients with increased baseline nasal resistance by10.6% (6.8%-14.3%). The change in nasal breathing epochs was inversely related to the change in snoring frequency (R s =0.503; pl0.001).  Nasal budesonide in snorers can modestly decrease snoring frequency and increase REM sleep.
Abstract P149: The Impact on HbA1c of Adherence Measured Over Multiple Short Intervals: A More Direct Assessment of Biologic Response
Authors: Gregory A Nichols, A G Rosales, Teresa M Kimes, Kaan Tunceli, Karen Kurtyka, Panagiotis Mavros, John F Steiner
Journal: Circulation (2015)

Adherence to medications is typically estimated over a 6-12 month period and associated with a mean biologic response over a similar timeframe. Our objective was to examine the relationship between a specific HbA1c measurement and a measure of adherence calculated from medication dispenses over the preceding 90 days among patients who newly initiated metformin therapy.We identified 3,109 persons with type 2 diabetes who initiated metformin as their first ever anti-hyperglycemic drug, analyzing all 9,918 HbA1c measurements that occurred over the next 2 years. We used an adaptation of the proportion of days covered method for assessing medication adherence that corresponded to an approximate 90-day interval preceding an HbA1c measurement, terming the adaptation the “interval-based proportion of days covered” (IB-PDC). To account for multiple observations per patient, we analyzed the association between HbA1c and IB-PDC within the generalized estimating equation (GEE) framework. Analyses were stratified by HbA1c prior to metformin initiation using a cut-point of 8%.  After multivariable adjustment using 0% adherence as the reference category, IB-PDC 1-49% was not associated with HbA1c. However, IB-PDC 50-79% was associated with lower HbA1c values of 0.113 (95% CI: 0.025, 0.202) percentage points among patients with pre-metformin HbA1c  8% at metformin initiation. IB-PDC >80% was associated with lower HbA1c of 0.175 (0.093, 0.257) and 0.453 (0.320, 0.586) percentage points for those with HbA1c  8%, respectively. When re-categorizing IB-PDC into 10% bands using 0-49% as the reference category, HbA1c associated with IB-PDC 50-59% were not significantly different. Among patients with HbA1c  90% was associated with lower HbA1c 0.151 percentage points (95% CI 0.087, 0.216) compared with IB-PDC   8%, where IB-PDC 80-89% was associated with HbA1c that was 0.534 (0.403, 0.666) percentage points lower than the reference category.  Using this novel short-interval approach that more closely associates the effects of adherence with the expected biologic response, better medication adherence in obtaining prescriptions was associated with lower HbA1c levels than has been previously reported. The impact of this adherence measure on glycemic control was dependent upon the HbA1c level prior to initiating metformin.
Phase II study of paclitaxel in relapsed non-Hodgkin's lymphomas.
Authors: W H Wilson, B A Chabner, G Bryant, S Bates, A Fojo, J Regis, E S Jaffe, S M Steinberg, B R Goldspiel, B D Cheson
Journal: Journal of Clinical Oncology (1995)

PURPOSE To assess the efficacy and toxicity of paclitaxel administered as a 96-hour infusion to patients with relapsed non-Hodgkin's lymphomas (NHLs). PATIENTS AND METHODS Eligible patients had relapsed NHL and measurable disease and were considered incurable. Paclitaxel was infused at a dose of 140 mg/m2 every 3 weeks. Premedications to prevent paclitaxel hypersensitivity reactions were not administered and no patients received corticosteroids. Expression of the multidrug resistance (mdr-1) gene was determined in tumor from 17 patients by mRNA quantitative polymerase chain reaction (PCR). RESULTS Thirty-one patients received a total of 99 cycles of paclitaxel. Two patients were not assessable for response. The median age was 50 years, 71% had stage IV disease, and intermediate/high-grade histology was present in 65% of patients. Patients had received a median of three prior chemotherapy regimens, and 68% of patients had responded to the previous chemotherapy (chemotherapy-sensitive). Of 29 assessable patients, five (17%) achieved a partial response (PR). With a median potential follow-up time of 17 months, the median event-free and overall survival durations were 1.6 and 7.5 months, respectively. No correlation was found between response to paclitaxel and extent of prior treatment or response. The mdr-1 gene was easily detectable in 14 of 17 tumor biopsies, but was low in all but one sample. The most serious toxicity was grade 4 neutropenia, which occurred during 14% of cycles. CONCLUSION Paclitaxel was well tolerated, but had a low response rate in patients with relapsed NHLs. There was no clear association between response to paclitaxel and extent of our response to prior treatment. Most patients had chemotherapy-sensitive disease, which suggests that the low response rate to paclitaxel was probably not due to general chemotherapy resistance. Paclitaxel provided good palliation in a minority of patients and is a reasonable agent to consider for use in patients who have failed to respond to standard chemotherapy.
Associations of Cancer Site and Type With Occupation and Industry From the Third National Cancer Survey Interview
Authors: Roger R. Williams, Nancy L. Stegens, John R. Goldsmith
Journal: JNCI Journal of the National Cancer Institute (1977)

From the Third National Cancer Survey (TNCS) Interview Study of 7,518 incident cases, lifetime histories of occupations and industries were studied for associations with specific cancer sites and types while controlling for age, sex, race, education, use of cigarettes or alcohol, and geographic location. Lung cancer patients were found more often than expected among several categories including trucking, air transportation, wholesaling, painting, building construction, building maintenance, and manufacturing (furniture, transportation equipment, and food products). Controlling for cigarette smoking did not change these associations. Leukemia and multiple myeloma were associated with sales personnel of both sexes, whereas lymphomas and Hodgkin's disease were excessive among women working in the medical industry. Other associations included rectal cancer with several retail industries; prostate cancer with ministers, farmers, plumbers, and coal miners; malignant melanoma with school teachers; and invasive cervical cancer with women working in hotels and restaurants. Breast cancer patients were more common among women who were teachers or other professionals and who worked in business and finance (even after controlling for education). Many other findings are presented in detailed tables. Results are reported mainly as a research resource for use by other investigators doing work in this field. Suggestions are given for future studies.
Carcinogenicity of &lt;italic&gt;o&lt;/italic&gt;-Ethoxybenzamide in (C57BL/6N × C3H/HeN)F&lt;sub&gt;1&lt;/sub&gt; Mice&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: M Naito, A Ito, H Watanabe, K Kawashima, H Aoyama
Journal: JNCI Journal of the National Cancer Institute (1986)

The carcinogenicity of o-ethoxybenzamide (CAS: 938-73-8), which is also called ethenzamide and which is widely used as an antipyretic anodyne in Japan, was examined in 298 (C57BL/6N X C3H/HeN)F1 mice. Groups of males and females were fed a diet containing 0 (control), 0.4, or 1.2% o-ethoxybenzamide for 96 weeks and sacrificed at the 100th week. Among the male mice fed the higher dose of the drug, the total incidence of liver cell tumors was 68%, with 18% of the mice developing hepatocellular carcinomas; both yields were significantly higher than those in the controls. In o-ethoxybenzamide-treated male mice the multiplicities of the hepatic cell tumors were also significantly higher than the multiplicity of the hepatic tumor in male control mice. A dose-response relationship with regard to both incidence and multiplicities of hepatic cell tumors in male mice was observed. In female mice fed o-ethoxybenzamide the incidence and multiplicities of the liver cell tumors were increased compared to those of the controls, but statistical significance was observed only in the multiplicity of tumors in mice given the lower dose. In both sexes hepatic cell tumors developed earlier than in the controls. These results show that o-ethoxybenzamide enhances the development of hepatic cell tumors in male (C57BL/6N X C3H/HeN)F1 mice.
Stable Heat-Resistant Variants in Populations of Chinese Hamster Cells2
Authors: Morgan Harris
Journal: JNCI Journal of the National Cancer Institute (1980)

Sublines with increased survival at elevated temperatures were obtained by repeated exposure of V79 Chinese hamster lung cells to 44.5 degrees C followed by regrowth of survivors to mass populations at 37 degrees C. After three cycles, the time at 44.5 degrees C required to reduce cell survival to 37% (D0 value) increased from 4.6 to 26.3 minutes. Clonal isolates retained their resistance to thermal stress for at least 3 months in culture at 37 degrees C and showed distinctive differences from precursor cells in growth rate and colonial morphology. These differences disappeared in hybrids constructed between resistant and sensitive cells. In assays of 44.5 degrees C, hybrid survival was only slightly increased over levels obtained with sensitive cells. Heat resistance and associated marker characteristics thus appear to be recessive or weakly codominant. Cytohybrids were also constructed by fusing cytoplasts from sensitive cells to nucleated heat-resistant cells. No cytoplasmic transfer of marker characteristics was detected in these combinations, which suggests that controls for heat resistance are nuclear in origin.
Early life tobacco smoke exposure is associated with asthma and lung function deficits in adolescents
Authors: Xu Dai, S. Dharmage, Adrian Lowe, Katrina Allen, Paul Thomas, Jennifer Perret, David Hill, Clifford Hosking, John Hopper, Melanie Matheson, Cecilie Svanes, Liam Welsh, Michael Abramson, Caroline Lodge
Journal: European Respiratory Journal (2014)

Background:  Parental smoking is associated with asthma and impaired lung function during early childhood. Less is known about the impact of early life smoke exposure on asthma, lung function and lung function growth into adolescence.   Objective:  To determine the association between perinatal smoke exposure and lung function and asthma up to18 years.   Method:  The Melbourne Atopy Cohort Study (MACS), a high-risk birth cohort (n= 620), recorded parental smoking at baseline and respiratory outcomes including spirometry at 12 and 18 years. Multiple logistic regression was used to analyse the associations between perinatal smoking and reported asthma at 12 (n=370) and 18 years (n=411). Multiple linear regression assessed the effect of perinatal smoking on lung function at 12 and 18 years and lung function growth between 12 and 18 years.   Results:  At 18 years, girls exposed to parental smoking in the perinatal period had increased odds of asthma (OR: 3.45, 95%CI: 1.36, 8.77) and reduced: pre-bronchodilator FEV 1  (decreased by 214, 95%CI: 39, 389 ml); FEV 1 /FVC ratio (deceased by 0.077, 95%CI: 0.017, 0.138); and MEF 25-75  (reduced by 430, 95%CI: 61, 798 ml/s), as well as reduced post bronchodilator FEV 1 /FVC (decreased by 0.073, 95%CI: 0.018, 0.128). No associations seen for boys. Furthermore, impairment of lung function growth in pre-bronchodilator FEV 1  between 12 and 18 years was associated with early life maternal smoking, (reduced by 261, 95%CI: 20, 502 ml) independent of gender.   Conclusion:  Perinatal smoke exposure is associated with increased risk of asthma, reduced lung function and reduced lung function growth in adolescence. Adolescent girls appear to be more susceptible than boys.
Utility of bronchoscopy in the rapid diagnosis of miliary tuberculosis
Authors: Pilar Sanjuán López, Marina Blanco Aparicio, Iria Vidal García, Carmen Montero Martínez
Journal: European Respiratory Journal (2014)

In miliary tuberculosis (TB) sputum smear is often negative or no sample is obtained, this means the need for invasive techniques

AIM: Communicate our experience with the yield of bronchoscopy in rapid diagnosis of miliary TB

METHODS: Retrospective study of patients diagnosed with miliary TB with at least 1 bronchoscopy between 1995-2011. Definitive diagnosis: 1) culture of M. tuberculosis in any sample 2) caseating granuloma in biopsy, with or without Ziehl-Neelsen positive 3) response to treatment for TB. Rapid diagnosis: sputum smear positive or necrotizing granulomas.

RESULTS: 42 patients identified. 43% women. Mean age: 46.2 + 8 years. Risk factors for miliary TB: HIV 12%; Alcoholism/hepatic disease 23%; Diabetes mellitus 10%, Immunosuppressive drugs 17%; older than 70 years 17%; others 21%. Diagnostic methods: 20 (48%) patients had spontaneous sputum and culture was positive in 12 (60%). Sputum was induced in 2 (4.8%): stain was negative and culture positive in one.

View this table:

Table 1: yield of bronchoscopic samples





Rapid diagnosis by bronchoscopy was reached in 24 (57%) cases and definitive diagnosis in 35 (83%).

CONCLUSIONS: the smears of the BAS and BAL have low diagnostic yield. Transbronchial biopsy is the technique of choice for rapid diagnosis of miliary TB and we recommend its systematic implementation if the risk is acceptable.
Effects of Continuous Positive Airway Pressure Therapy Withdrawal in Patients with Obstructive Sleep Apnea
Authors: Malcolm Kohler, Anne-Christin Stoewhas, Lisa Ayers, Oliver Senn, Konrad E. Bloch, Erich W. Russi, John R. Stradling
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Rationale: To establish a new approach to investigate the physiological effects of obstructive sleep apnea (OSA), and to evaluate novel treatments, during a period of continuous positive airway pressure (CPAP) withdrawal.Objectives: To determine the effects of CPAP withdrawal.Methods: Forty-one patients with OSA and receiving CPAP were randomized to either CPAP withdrawal (subtherapeutic CPAP), or continued CPAP, for 2 weeks. Polysomnography, sleepiness, psychomotor performance, endothelial function, blood pressure (BP), heart rate (HR), urinary catecholamines, blood markers of systemic inflammation, and metabolism were assessed.Measurements and Main Results: CPAP withdrawal led to a recurrence of OSA within a few days and a return of subjective sleepiness, but was not associated with significant deterioration of psychomotor performance within 2 weeks. Endothelial function, assessed by flow-mediated dilatation, decreased significantly in the CPAP withdrawal group compared with therapeutic CPAP (mean difference in change, –3.2%; 95% confidence interval [CI], –4.5, –1.9%; P < 0.001). Compared with continuing CPAP, 2 weeks of CPAP withdrawal was associated with a significant increase in morning systolic BP (mean difference in change, +8.5 mm Hg; 95% CI, +1.7, +15.3 mm Hg; P = 0.016), morning diastolic BP (mean difference in change, +6.9 mm Hg; 95% CI, +1.9, +11.9 mm Hg; P = 0.008), and morning HR (mean difference in change, +6.3 bpm, 95% CI, +0.4, +12.2 bpm; P = 0.035). CPAP withdrawal was associated with an increase in urinary catecholamines but did not lead to an increase in markers of systemic inflammation, insulin resistance, or blood lipids.Conclusions: CPAP withdrawal usually leads to a rapid recurrence of OSA, a return of subjective sleepiness, and is associated with impaired endothelial function, increased urinary catecholamines, blood pressure, and heart rate. Thus the proposed study model appears to be suitable to evaluate physiological and therapeutic effects in OSA.Clinical trial registered with www.controlled-trials.com (ISRCTN 93153804).