tbuckley/cabot-search huggingface dataset:
The epidemiology of respiratory tract pathogens in southern Netherlands
Authors: BI Davies, FP Maesen
Journal: European Respiratory Journal (1988)

Results of sputum cultures and susceptibility tests have been reviewed for the years 1977-1986, with approximately 1,700 positive cultures per year. Haemophilus influenzae always occupied the first place, being grown in 65% of positive specimens in 1977 and 37% in 1986. Streptococcus pneumoniae occupied the second place, rising from 17 to 27% in the same period, during which Branhamella catarrhalis rose from 5 to 26%. Based on the frequency of occurrence of individual bacterial species in the sputum cultures and on the percentage of strains resistant to ampicillin, cotrimoxazole, doxycycline, erythromycin and ofloxacin, theoretical chances of failure of blind therapy were calculated and found to be most advantageous for ofloxacin and cotrimoxazole. No explanation could be given for the increase in beta-lactamase production by B. catarrhalis, but the disappearance of Haemophilus parainfluenzae may have been due to improvements in the identification procedure.
Chromosome Numbers of Normal and Preneoplastic Mouse Mammary Tissues Grown &lt;italic&gt;In Vivo&lt;/italic&gt; After Monolayer Culture&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Charles W. Daniel, Kathleen Church
Journal: JNCI Journal of the National Cancer Institute (1968)

Chromosome counts were made from normal mammary tissue and from a precancerous, hyperplastic mammary tissue; both were almost exclusively diploid. When placed in short-term cell culture, however, about 10% of both the normal and preneoplastic cells studied were heteroploid. Samples of these monolayer cultures were implanted into the mammarygland-free fat pads of isogenic mice to determine if these heteroploid cells would be maintained, or selected for or against, during a subsequent period of growth in vivo. After a growth period of 3–5 months several fat pads containing culture-derived outgrowths were studied. Five outgrowths derived from cultured normal gland contained no heteroploid cells and therefore resembled control outgrowths. In contrast, six outgrowths originating from cultured preneoplastic tissue displayed a marked shift in ploidy, with heteroploid frequencies ranging from a low of 50% to a high of 98%.
Esmolol is safer than and as effective as labetalol
Authors: B O'Connor, J B Luntley
Journal: BMJ (1995)

Expression of the inducible isoform of nitric oxide synthase (iNOS) and generation of nitric oxide (NO) have been recently described, in addition to mesangial and medullary thick ascending limb cells, in proximal tubular cells, including MCT, a mouse proximal tubular epithelium cell line. Because vasoconstrictors may interfere with the induction of iNOS and the subsequent generation of NO, in the study presented here, whether exogenous angiotensin II (ANG II) influences bacterial lipopolysaccharide (LPS)/gamma-interferon (gamma-IF)-stimulated NO synthesis and iNOS protein and mRNA expression in MCT cells was tested. LPS/gamma-IF readily stimulated nitrite synthesis in MCT cells, as one measured parameter of NO synthesis. Coincubation of cells with 10(-9)-10(-6) M ANG II attenuated this LPS/gamma-IF-stimulated induction of nitrite. This effect was reversed by the AT1-receptor blocker losartan, but not by an AT2-receptor antagonist, indicating signal transduction through AT1-receptors. Western blot analysis applying a specific monoclonal antibody generated against mouse iNOS revealed that 10(-8)-10(-6) M ANG II significantly reduced LPS/gamma-IF-induced iNOS protein expression. However, ANG II had no effect on LPS/gamma-IF-induced iNOS mRNA as assessed by Northern blots. Moreover, transient transfection studies using a chimeric gene construct, in which iNOS regulatory elements are linked to the CAT reporter gene, showed no effect of ANG II on the LPS/gamma-IF-stimulated transcriptional activity. The study presented here demonstrates that ANG II influences LPS/gamma-IF-stimulated NO generation in MCT cells, most likely at a posttranscriptional level, by influencing iNOS protein expression. Whether proximal tubular cells in vivo express iNOS remains to be established, but this study suggests a mechanism for how iNOS activity is influenced by ANG II in cultured proximal tubular cells.
Comparison of one week of oral terbinafine (250 mg/day) with four weeks of treatment with clotrimazole 1% cream in interdigital tinea pedis
Authors: None StC.Barnetson, None Marley, None Bullen, None Brookman, None Cowen, None Ellis, None Williams
Journal: British Journal of Dermatology (1998)

Treatment of interdigital tinea pedis often involves long-term therapy with topically applied preparations. Effective oral preparations, such as the allylamine terbinafine (Lamisil), taken over a shorter period, could provide a useful therapeutic alternative. A total of 269 patients from five centres with clinically diagnosed interdigital tinea pedis were entered into this double-blind, randomized, double-dummy, parallel-group study comparing oral terbinafine 250 mg once daily for 1 week with 1% clotrimazole (Canesten) cream applied twice daily for 4 weeks. Of these, 137 patients were evaluable for efficacy (confirmed dermatophyte infection by microscopy and culture): 63 terbinafine and 74 clotrimazole. At week 4, the mycological cure rates (negative culture at week 1 and negative results on microscopy and culture at week 4 onwards) were very similar (71% for clotrimazole and 72% for terbinafine). There was a faster response rate in the terbinafine group with respect to signs and symptoms at week 1. Both treatments were equally well tolerated; adverse events occurred equally in the two groups. In conclusion, oral terbinafine in a single daily dose of 250 mg for 1 week is as effective and as well tolerated as 1% clotrimazole cream applied twice daily for 4 weeks in the treatment of interdigital tinea pedis.
Phase I dose-escalation study of the PI3K/mTOR inhibitor voxtalisib (SAR245409, XL765) plus temozolomide with or without radiotherapy in patients with high-grade glioma
Authors: Patrick Y. Wen, Antonio Omuro, Manmeet S. Ahluwalia, Hassan M. Fathallah-Shaykh, Nimish Mohile, Joanne J. Lager, A. Douglas Laird, Jiali Tang, Jason Jiang, Coumaran Egile, Timothy F. Cloughesy
Journal: Neuro-Oncology (2015)

This phase I study aimed to evaluate safety, maximum tolerated dose, pharmacokinetics, pharmacodynamics, and preliminary efficacy of voxtalisib (SAR245409, XL765), a pan-class I phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) inhibitor, in combination with temozolomide (TMZ), with or without radiation therapy (RT), in patients with high-grade glioma. Patients received voxtalisib 30–90 mg once daily (q.d.) or 20–50 mg twice daily (b.i.d.), in combination with 200 mg/m2 TMZ (n = 49), or voxtalisib 20 mg q.d. with 75 mg/m2 TMZ and RT (n = 5). A standard 3 + 3 dose-escalation design was used to determine the maximum tolerated dose. Patients were evaluated for adverse events (AEs), plasma pharmacokinetics, pharmacodynamic effects in skin biopsies, and tumor response. The maximum tolerated doses were 90 mg q.d. and 40 mg b.i.d. for voxtalisib in combination with TMZ. The most frequently reported treatment-related AEs were nausea (48%), fatigue (43%), thrombocytopenia (26%), and diarrhea (24%). The most frequently reported treatment-related grade ≥3 AEs were lymphopenia (13%), thrombocytopenia, and decreased platelet count (9% each). Pharmacokinetic parameters were similar to previous studies with voxtalisib monotherapy. Moderate inhibition of PI3K signaling was observed in skin biopsies. Best response was partial response in 4% of evaluable patients, with stable disease observed in 68%. Voxtalisib in combination with TMZ with or without RT in patients with high-grade gliomas demonstrated a favorable safety profile and a moderate level of PI3K/mTOR pathway inhibition.
Phase I study of taxol and granulocyte colony-stimulating factor in patients with refractory ovarian cancer.
Authors: G Sarosy, E Kohn, D A Stone, M Rothenberg, J Jacob, D O Adamo, F P Ognibene, R E Cunnion, E Reed
Journal: Journal of Clinical Oncology (1992)

PURPOSE To increase the taxol dose beyond the current standard dose intensity of 175 mg/m2 per 21 days in patients with refractory ovarian cancer. PATIENTS AND METHODS Fifteen patients who had platinum-refractory or recurrent advanced-stage ovarian cancer were treated with taxol in a phase I trial and were given granulocyte-colony stimulating factor (G-CSF). Taxol was administered at doses of 170, 200, 250, and 300 mg/m2 every 3 weeks. G-CSF was given as a daily subcutaneous injection that started 24 hours after the completion of the taxol infusion. RESULTS Four patients required either taxol dose reduction or delay. The dose-limiting toxicity (DLT) was peripheral neuropathy, and it occurred at 300 mg/m2. This toxicity was manifested clinically as a stocking-and-glove sensory disturbance that primarily affected proprioception, and was associated with objective changes on nerve conduction studies in affected individuals. Mucositis was rarely observed. Substantial myelosuppression was observed, but was not dose-limiting. Five of 14 assessable patients experienced an objective response to therapy, with another five individuals who experienced a 30% to 45% reduction in tumor mass. CONCLUSION Taxol can be safely administered in doses up to 250 mg/m2 with G-CSF support, which may make it possible to study taxol dose intensification.
Roflumilast N-oxide, a selective PDE4 inhibitor, curbs platelet-leukocyte interactions
Authors: Licia Totani, Antonio Piccoli, Concetta Amore, Angelomaria Di Santo, Nicola Martelli, Giuseppe Dell'Elba, Virgilio Evangelista
Journal: European Respiratory Journal (2011)

Objective:  COPD is associated with cardiovascular comorbidities. Platelet (Plt)–leukocyte interactions play a role in vascular disease. We tested the effect of the PDE4 inhibitor roflumilast N-oxide (RNO), the active metabolite of roflumilast approved for severe COPD in EU, on Plt-mediated neutrophil (Neu) recruitment and tissue factor (TF) expression in monocytes (Mn).   Methods:  Neu adhesion to spread Plt or endothelium (EC) and Plt-induced TF in Mn were analysed with RNO with or without formoterol (F) (100 nM).*p   Results:  In a flow adhesion assay RNO, alone or with F, concentration-dependently reduced the number of Neu firmly adhered on spread Plt at 10 dynes/cm 2  shear stress (C 106±18 and RNO [100nM] 71±7*; F 110±11 and RNO&F 58±7* Neu per field). RNO also inhibited P-selectin (C 59±11, RNO 35±7*, F 65±13, RNO&F 16±4* Neu per field) and Plt-induced (C 49±2, RNO 12±2*, F 50±11, RNO&F 2±0* Neu per field) Neu recruitment on EC. Src kinases and downstream effectors Pyk2 and PI(3)K mediate P-selectin-triggered PSGL-1-Mac-1 cross-talk. RNO curbed Src-mediated Pyk2 phosphorylation and PI3K-mediated Akt phosphorylation, while inducing phosphorylation of Csk, the major negative regulator of Src, by protein kinase A. In Mn exposed to activated Plt (24h), RNO dose-dependently reduced TF activity (C 67±7, F 56±6, RNO [100nM] 9.7±3.9*, RNO&F 2±0.8*, arbitrary units). In the presence of F, RNO at 1nM reduced TF activity to 24.5±7.8*. RNO (100nM) also reduced TF mRNA (C 72±10, RNO 9±3 fold increase).   Conclusion:  The PDE4 inhibitor RNO curbs Plt–leukocyte interactions.
Age frequency distribution of joint ER/PR phenotypes in primary breast cancer patients: An analysis of 3,620 cases at a single Japanese institute
Authors: S. Saji, N. Ishizuka, K. Horiguchi, E. Suzuki, H. Bando, T. Aruga, I. Takahashi, T. Tominaga, M. Toi
Journal: Journal of Clinical Oncology (2006)

597 Background: Hormone receptor (HR) expression may reflect the different subtypes of breast cancer. Recent clinical trials have reported that joint Estrogen receptor (ER)/Progesterone receptor (PR) phenotypes in breast cancer have specific spectrum for treatment response. To analyze the epidemiologic character of ER/PR subtypes in Japanese patients, a retrospective data survey was conducted for 3,620 breast cancer patients treated at a single institute during 1975–2005. Methods: Patients records were obtained from cancer registration of the Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital and analyzed with SAS software. Among 3,620 operated patients, data of ER/PR subtypes were available in 2,707 cases. HRs were evaluated by ligand binding assay (LBA) or enzyme immuno assay (EIA) from 1975 to 2000 (n=1721), and by immunohistochemistry (IHC) after that (n=986). Results: Both mean and median of patient’s age increased through the operated year (p&lt;0.0001). Therefore, all analysis related to distribution of age were adjusted by the operated year. As reported before, ER+ population showed liner trend with age by LBA/EIA (p&lt;0.0001), while this was not observed by IHC. ER-/PR+ population was 10.6% by LBA/EIA, whereas it decreased to 2.1% by IHC. These are due to the increase of ER+ population with IHC analysis, since marginal distribution between two methods in the patients tested by both assays was significantly different for ER, but not for PR (n=181, p=0.0038 and n=175, p=0.1944). Irrespective of assay methods, peak age frequency of ER+/PR+ was between 46 and 50 years of age, whereas that of ER+/PR- was 56–60. For ER/PR phenotypes there was a significant difference of odds ratio across the age (&lt;55 vs. ≥55, p=0.04 for IHC, p=0.0002 for LBA/EIA). Conclusion: Changes of standard assay from LBA/EIA to IHC affected the population of ER+ and lead the decrease of ER-/PR+ subtype. Japanese women’s peak age frequency of ER+/PR+ was in the premenopausal period compared to that of non-Hispanic white women in the postmenopausal age (Anderson WF, JCO 2001). Difference of most frequent age of each subtype among the races may be taken into account for the development of chemoprevention strategy with anti-estrogens. No significant financial relationships to disclose.
The Effect of Dietary 2-Acetylaminofluorene on the Uracil-degrading Enzymes in Rat Liver
Authors: P Fritzson, J Efskind
Journal: Cancer Research (1965)

The activities of the uracil-degrading liver enzymes, uracil reductase (EC 1.3.1.2), dihydrouracil hydrolase (EC 3.5.2.2), and carbamoyl-β-alanine hydrolase (EC 3.5.1.6) have been determined in rats fed 2 different basal diets supplemented with the carcinogen 2-acetylaminofluorene for various lengths of time. A fall in the activities of all 3 enzymes occurred in the preneoplastic liver during carcinogen feeding. It was most pronounced in the case of uracil reductase, the enzyme which limits uracil breakdown in rat liver. The activities of uracil reductase and carbamoyl-β-alanine hydrolase reached the minimum level in about 30 days. The dihydrouracil hydrolase activity decreased still more slowly. The enzymes remained at the low activity level or increased slowly in activity during continued carcinogen feeding. Removal of the carcinogen after 90 days resulted in almost complete recovery of the activities of all 3 enzymes.

With dietary supplements of 0.03 and 0.05% 2-acetylaminofluorene, the decrease in uracil reductase activity was proportional to the amount of carcinogen in the diet, the minimum level being about 50% of the control. The decrease in enzyme activity was the same with the 2 different basal diets, even though the rate of occurrence of malignant transformation was strikingly different with the 2 diets.

The results are discussed in relation to uracil incorporation into RNA,[3][1] and to liver carcinogenesis. Possible factors responsible for the decrease in enzyme activity are considered.

 [1]: #fn-3
Can probiotic yogurt prevent diarrhoea in children on antibiotics? A double-blind, randomised, placebo-controlled study
Authors: MJ Fox, Kdk Ahuja, IK Robertson, MJ Ball, RD Eri
Journal: BMJ (2015)

Objective: 

To estimate the efficacy of a probiotic yogurt compared to a pasteurised yogurt for the prevention of antibiotic-associated diarrhoea in children.  Design and setting: 

This was a multisite, randomised, double-blind, placebo-controlled clinical trial conducted between September 2009 and 2012. The study was conducted through general practices and pharmacies in Launceston, Tasmania, Australia.  Participants and interventions: 

Children (aged 1–12 years) prescribed antibiotics, were randomised to receive 200 g/day of either yogurt (probiotic) containing lactis (Bb-12) and Lactobacillus acidophilus (La-5) or a pasteurised yogurt (placebo) for the same duration as their antibiotic treatment.  Outcomes: 

Stool frequency and consistency were recorded for the duration of treatment plus 1 week. Primary outcome was stool frequency and consistency, classified at different levels of diarrhoea severity. Due to the small number of cases of diarrhoea, comparisons between groups were made using Fisher's exact analysis.  Results: 

72 children commenced and 70 children (36 placebo and 34 probiotic) completed the trial. There were no incidents of severe diarrhoea (stool consistency ≥ 6, ≥ 3 stools/day for ≥ 2 consecutive days) in the probiotic group and six in the placebo group (Fisher's exact p = 0.025). There was also only one episode of minor diarrhoea (stool consistency ≥ 5, ≥ 2 stools/day for ≥ 2 days in the probiotic group compared to 21 in the placebo group (Fisher's exact p   Conclusions: 

A yogurt combination of LGG, La-5 and Bb-12 is an effective method for reducing the incidence of antibiotic-associated diarrhoea in children.
Asbestos-related disorders (ARDs): Influence of pleural plaques and pulmonary fibrosis due to asbestos exposure on lung function decline (LFD)
Authors: Heiko Knoop, Phil Marlon Million, Andreas Weber, Fabian Wolter, Jürgen Behr
Journal: European Respiratory Journal (2014)

Introduction   Pulmonary fibrosis due to asbestos exposure (PFDAE) and UIP (Usual Interstitial Pneumonia) eventually show similar radiological patterns. While LFD in UIP has been well characterized, data on deterioration in pulmonary function tests (PFT) in PFDAE are limited.   Methodology   Determination of the deterioration in PFT in patients with ARD (patients (P) n=56; 54 with Thorax CT-scan. Median linear progression (MLP)/y of FVC, TLC and DLCO SB  were generated and evaluated in relation to predominant manifestation of asbestosis (Pleural plaques (PP); PFDAE; mixed type (MT)). For quantification of PP and PFDAE, thoracic CT-scans were performed to distinguish three entities: PP-type=PFDAE/PP   Results   In ARDs, LFD was observed in all patients during follow-up. The PFDAE-type was associated with highest rate of MLP, followed by MT and PP-type (TLC, DLCO SB ). However, MLP for FVC was highest in MT, followed by PFDAE- and PP-type (see table).   Conclusion   ARDs with mainly fibrotic manifestation show higher PFT progression rates than those with predominant pleural manifestation. CT-Scans were not performed at identical intervals of follow-up, which might be a confounding factor. For future evaluation of LFD in ARDs, prospective studies are warranted.
Self-reported race and ethnicity affect FeNO values in healthy individuals
Authors: Tiago Jacinto, Andrei Malinovschi, Christer Janson, João Fonseca, Kjell Alving
Journal: European Respiratory Journal (2012)

Background: Race and ethnicity are known factors of variation in pulmonary function. We aim to determine if self-identified race/ethnicity affect the values of exhaled nitric oxide (FeNO) in healthy and asthmatic individuals in a population setting.  Methods: We analyzed the valid FeNO measurements (NIOX MINO) recorded in the National Health and Nutrition Examination Survey 2007-10 (n=13,275; age 6-79 years). Race/ethnicity is coded as Mexican American (20%), Other Hispanic (11%), Non-Hispanic White (43%), Non-Hispanic Black (20%) and Other Race - Inc. Multi-Racial (5%). Adjustments were made using multiple-linear regression models.  Results: Non-Hispanic Whites have the lowest FeNO values (mean 15.8 ppb, 95%CI 15.4; 16.1) and Other Race - Including Multi-Racial the highest (20.0 ppb (18.6; 21.4)). Race and ethnicity significantly affect FeNO values even after adjusting for age, gender, BMI and reported hay fever in non-asthmatic subjects (B=0.30, p=0.01), but not in individuals with self-reported asthma (B=0.09, p=0.83). However, the mean difference between race/ethnicity categories was reduced after excluding subjects with hay fever.  Conclusion: Race and ethnicity are significant factors for FeNO in healthy individuals. Hay fever seems to play an important role in the mean difference between race/ethnicity categories. An objective measurement of atopy is probably needed to clarify this relationship.
Long-term regulation of renal urea transporter protein expression in rat.
Authors: J Terris, C A Ecelbarger, J M Sands, M A Knepper
Journal: Journal of the American Society of Nephrology (1998)

To test the hypothesis that the abundance of the apical urea transporter of the inner medullary collecting duct (IMCD) is regulated in vivo by factors associated with altered water balance, immunoblots of rat inner medullary membrane fractions were probed with rabbit polyclonal antibodies against the renal urea transporter (RUT) gene product. In inner medullas of Brattleboro rats, which manifest severe chronic water diuresis, a 117-kD band was seen, in addition to the previously described 97-kD band. These two bands were detectable by antibodies directed against two different regions of the RUT sequence. When Brattleboro rats were treated with a 5-d infusion of arginine vasopressin (AVP) by osmotic minipump, the 117-kD band was markedly diminished, whereas the 97-kD band was unchanged. Simultaneous infusion of the diuretic agent furosemide prevented the AVP-induced decrease in the 117-kD band. In AVP-infused Sprague Dawley rats, the 117-kD band was barely perceptible. However, when AVP-treated rats were infused with furosemide for 5 d, the 117-kD band was markedly accentuated, whereas the 97-kD band was unchanged. The abundance of the 117-kD RUT protein in the renal papilla was inversely correlated with dietary protein intake. Further immunoblotting studies revealed that the 117-kD protein is heavily expressed in IMCD cells and not in non-collecting duct components of the inner medulla, and is present in low-density microsome fractions from inner medulla. From this study, the following conclusions can be made: (1) The collecting duct urea transporter is present in at least two forms (97 and 117 kD) in the IMCD. (2) The expression level of the 117-kD urea transporter protein is regulated and is inversely correlated with medullary osmolality and urea concentration, but does not correlate with circulating AVP level. (3) Although AVP regulates RUT function on a short-term basis, long-term changes in AVP levels do not increase RUT abundance.
Oropharyngeal yeast colonization in HIV-infected outpatients in southern Taiwan: CD4 count, efavirenz therapy and intravenous drug use matter
Authors: C.-J. Wu, H.-C. Lee, Y.-L. Yang, C.-M. Chang, H.-T. Chen, C.-C. Lin, N.-Y. Lee, W.-L. Chu, L.-Y. Hsieh, Y.-L. Wang, T.-L. Lauderale, F.-C. Tseng, N.-Y. Ko, W.-C. Ko, H.-J. Lo
Journal: Clinical Microbiology and Infection (2011)