tbuckley/cabot-search huggingface dataset:
Sleepiness, Quality of Life, and Sleep Maintenance in REM versus non-REM Sleep-disordered Breathing
Authors: Hassan A. Chami, Carol M. Baldwin, Angela Silverman, Ying Zhang, David Rapoport, Naresh M. Punjabi, Daniel J. Gottlieb
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

The impact of REM-predominant sleep-disordered breathing (SDB) on sleepiness, quality of life (QOL), and sleep maintenance is uncertain.
First Unaffected Pregnancy Using Preimplantation Genetic Diagnosis for Sickle Cell Anemia
Authors: Kangpu Xu, Zhong Ming Shi, Lucinda L. Veeck, Mark R. Hughes, Zev Rosenwaks
Journal: JAMA (1999)

Context Sickle cell anemia is a common autosomal recessive disorder.However, preimplantation genetic diagnosis (PGD) for this severe genetic disorder previously has not been successful. ObjectiveTo achieve pregnancy with an unaffected embryo using in vitro fertilization (IVF) and PGD.Design Laboratory analysis of DNA from single cells obtained by biopsy from embryos in 2 IVF attempts, 1 in 1996 and 1 in 1997, to determine the genetic status of each embryo before intrauterine transfer.Setting University hospital in a large metropolitan area.Patients A couple, both carriers of the recessive mutation for sickle cell disease.Interventions Standard IVF treatment, intracytoplasmic sperm injection, embryo biopsy, single-cell polymerase chain reaction and DNA analyses, embryo transfer to uterus, pregnancy confirmation, and prenatal diagnosis by amniocentesis at 16.5 weeks' gestation.Main Outcome Measure DNA analysis of single blastomeres indicating whether embryos carried the sickle cell mutation, allowing only unaffected or carrier embryos to be transferred. ResultsThe first IVF attempt failed to produce a pregnancy.Of the 7 embryos analyzed in the second attempt, PGD indicated that 4 were normal and 2 were carriers; diagnosis was not possible in 1.Three embryos were transferred to the uterus on the fourth day after oocyte retrieval.A twin pregnancy was confirmed by ultrasonography, and subsequent amniocentesis revealed that both fetuses were unaffected and were not carriers of the sickle cell mutation.The patient delivered healthy twins at 39 weeks' gestation. ConclusionThis first unaffected pregnancy resulting from PGD for sickle cell anemia demonstrates that the technique can be a powerful diagnostic tool for carrier couples who desire a healthy child but wish to avoid the difficult decision of whether to abort an affected fetus.
Empty Slogan for the Dying
Authors: F.J. Ingelfinger
Journal: New England Journal of Medicine (1974)

Paul Ramsey recently wrote an article entitled, "The Indignity of 'Death With Dignity.'"1 It is a title that is not only "extraordinary" but accurate. Brilliant dialectitian that he is, Ramsey examines his subject at various philosophical levels, some of them too deep for me to grasp. But there is no problem in understanding him when he writes, "There is an additional insult besides death itself heaped upon the dying by our ordinary talk about 'death with dignity.'" "Death with dignity" has indeed become tarnished; in its incessant iteration, the phrase (one is almost tempted to write DWD!) has become both . . .
Chronic non-A, non-B hepatitis: Ultrastructural and serologic studies
Authors: Francine Marciano-Cabral, Karen L. Rublee, Robert L. Carithers, Edward A. Galen, Thomas J. Sobieski, Guy A. Cabral
Journal: Hepatology (1981)

Liver biopsies from five patients with chronic non-A, non-B (NANB) hepatitis were examined by electron microscopy for hepatocellular alterations. Circular fused membranes were observed within the cytoplasm of hepatocytes of four of the patients. Aggregates of intranuclear particles, measuring 22 ± 2 nm in diameter, were also seen in two of the biopsies in which fused membranes were identified. Sera of all five patients formed precipitin lines detectable by counterimmunoelectrophoresis when reacted with serum from an individual convalescent from posttransfusion NANB hepatitis. Using this convalescent serum as an antibody source, complexes of 22 ± 2 nm particles were identified in three of the chronic patient sera by immunoelectron microscopy. These observations suggest that at least one of the agents responsible for NANB hepatitis elicits both nuclear and cytoplasmic modifications. Furthermore, the 22 ± 2 nm particles circulating in the sera of the chronic NANB patients may represent components related to NANB hepatitis agent.
Valve-in-a-Valve Concept for Transcatheter Minimally Invasive Repeat Xenograft Implantation
Authors: Thomas Walther, Volkmar Falk, Todd Dewey, Jörg Kempfert, Fabian Emrich, Bettina Pfannmüller, Petra Bröske, Michael A. Borger, Gerhard Schuler, Michael Mack, Friedrich W. Mohr
Journal: Journal of the American College of Cardiology (2007)
NHS services not improving as fast as investment, conference told
Authors: C. Shannon
Journal: BMJ (2003)

Britain's spending on health care is catching up with that of other industrialised nations, but simply throwing more tax money at the NHS will never improve services enough, a delegates at a conference on healthcare funding held last week in London were told. Greater use of the private sector–and more contributions from patients themselves–could be part of the answer.

In 2000 the prime minister, Tony Blair, promised to increase Britain's historically low spending on health care and match European levels of 8% of the gross domestic product within five years. Since then, “new” Labour has gone further and pledged that healthcare spending will reach 9.4% of the gross domestic product by 2007.

Latest available figures showed that the government was doing well on this promise. Healthcare spending as a proportion …
MALARIA CONTROL OPERATIONS IN RELATION TO THE ULTIMATE SUPPRESSION OF THE DISEASE
Authors: C. C. BASS
Journal: JAMA (1922)

In his book on "The Prevention of Malaria," Sir Ronald Ross<sup>1</sup>shows by elaborate mathematical calculations, and in quite a convincing way, that sufficient reduction in the anopheline density in a given area would ultimately result in the complete disappearance of malaria from the area without the reduction necessarily being carried to total elimination of anopheles. In other words, it is not necessary to secure 100 per cent, of anopheline control to secure 100 per cent, of control of transmission of malaria. This is based on the small proportion of the total number of anophelines produced, which chance to live long enough, bite favorable gamete carriers and later bite other susceptible individuals. In a large area, especially one not densely inhabited, there must be many thousands of anophelines produced, on an average, to one that actually transmits malaria. He argues, therefore, that, if the anopheline density is reduced to
Dopamine Transporter Genetic Variants and Pesticides in Parkinson’s Disease
Authors: Beate R. Ritz, Angelika D. Manthripragada, Sadie Costello, Sarah J. Lincoln, Matthew J. Farrer, Myles Cockburn, Jeff Bronstein
Journal: Environmental Health Perspectives (2009)

Research suggests that independent and joint effects of genetic variability in the dopamine transporter (DAT) locus and pesticides may influence Parkinson's disease (PD) risk.In 324 incident PD patients and 334 population controls from our rural California case-control study, we genotyped rs2652510, rs2550956 (for the DAT 5' clades), and the 3' variable number of tandem repeats (VNTR). Using geographic information system methods, we determined residential exposure to agricultural maneb and paraquat applications. We also collected occupational pesticide use data. Employing logistic regression, we calculated odds ratios (ORs) for clade diplotypes, VNTR genotype, and number of susceptibility (A clade and 9-repeat) alleles and assessed susceptibility allele-pesticide interactions.PD risk was increased separately in DAT A clade diplotype carriers [AA vs. BB: OR = 1.66; 95% confidence interval (CI), 1.08-2.57] and 3' VNTR 9/9 carriers (9/9 vs. 10/10: OR = 1.8; 95% CI, 0.96-3.57), and our data suggest a gene dosing effect. Importantly, high exposure to paraquat and maneb in carriers of one susceptibility allele increased PD risk 3-fold (OR = 2.99; 95% CI, 0.88-10.2), and in carriers of two or more alleles more than 4-fold (OR = 4.53; 95% CI, 1.70-12.1). We obtained similar results for occupational pesticide measures.Using two independent pesticide measures, we a) replicated previously reported gene-environment interactions between DAT genetic variants and occupational pesticide exposure in men and b) overcame previous limitations of nonspecific pesticide measures and potential recall bias by employing state records and computer models to estimate residential pesticide exposure.Our results suggest that DAT genetic variability and pesticide exposure interact to increase PD risk.
L-arginine normalizes endothelial function in cerebral vessels from hypercholesterolemic rabbits.
Authors: E Rossitch, E Alexander, P M Black, J P Cooke
Journal: Journal of Clinical Investigation (1991)

We hypothesized that normal vascular reactivity could be restored in vessels from hypercholesterolemic animals by exposing them to L-arginine, the precursor of endothelium-derived relaxing factor (EDRF). Basilar arteries were harvested from New Zealand white rabbits fed normal chow or that supplemented with 2% cholesterol for 10 wk. Vessels were cannulated for perfusion at physiologic pressure. Changes in vessel diameter were monitored by videomicroscopy. In comparison to normal vessels, those from hypercholesterolemic animals vasoconstricted more to KCl, endothelin (E), and 5-hydroxytryptamine (5-HT). Conversely, vasodilation to acetylcholine (ACh) (but not that to verapamil) was significantly impaired in the hypercholesterolemic animals. In vitro administration of L-arginine (3 mM) for 45 min normalized vasodilation to ACh and vasoconstriction to E, 5-HT, and KCl in the isolated vessels from hypercholesterolemic animals. This effect was stereospecific, since D-arginine had no effect. To conclude, these data confirm that hypercholesterolemia attenuates endothelium-derived relaxation, and enhances the sensitivity of these vessels to vasoconstrictors. In vitro administration of L-arginine normalized vascular reactivity of isolated vessels from hypercholesterolemic animals. Thus, hypercholesterolemia induces a reversible endothelial dysfunction that may be corrected by supplying the precursor of EDRF, L-arginine.
Six-month prognosis of patients diagnosed with myocardial infarction by World Health Organization criteria versus New European Society Cardiology/ American College Cardiology troponin-based criteria
Authors: Jasper Trevelyan, Mauro Lencioni, Shane Gieowarsingh, Edward W. Needham, Stephen C. Smith, Raj K. Mattu
Journal: Journal of the American College of Cardiology (2002)
Impact of PET and CT in PET/CT Studies for Staging and Evaluating Treatment Response in Bone and Soft Tissue Sarcomas
Authors: Elena Piperkova, Mounir Mikhaeil, Ali Mousavi, Richard Libes, Francisco Viejo-Rullan, Henry Lin, Gerald Rosen, Hussein Abdel-Dayem
Journal: Clinical Nuclear Medicine (2009)

Study impact of F-18 FDG PET/CT on initial staging, restaging, and evaluating treatment response (ETR) in bone and soft tissue sarcomas (BSTS), focusing on discrepancy between CT and PET portions.Ninety-three BSTS patients having 204 F-18 FDG PET/CT studies were retrospectively reviewed. They were divided into 4 groups. Group I for initial staging included 16 patient studies. The other 3 groups were divided according to the time interval from last treatment received. Group II for ETR up to 2 months included 83 studies. Group III was for early restaging after 2 to 6 months included 45 studies. Group IV was for long-term follow-up after 6 months included 60 studies. All results were confirmed either by pathology, or by clinical follow-up.Sixteen studies for initial staging were concordant in 14 and discordant in 2 patients (48 lesions, 46 concordant, and 2 discordant). PET showed 97.2% sensitivity and 100% specificity versus 100% and 91.6% on CT. Regarding the other 3 groups, 498 lesions were detected; PET and CT were concordant in 436/498 (88%) and discordant in 62/498 (12%). In group II for ETR, PET and CT were concordant in 64/83 (77%) and discordant in 19/83(23%) studies-13 showed excellent to complete response on PET with partial response (PR) or stable disease (SD) on CT; 6 studies in PET showed PR versus SD or progression of disease (PD) on CT. In group III, for early restaging of disease 36/45 (80%) concordant and 9/45 (20%) discordant (3 showed excellent to complete response and 2 PR on PET versus CT SD, 3 PET PR versus CT PD, and 1 PET study showed PD while CT showed SD). In group IV, for long-term restaging, 49/60 (82%) were concordant and 11/60 (18%) were discordant; 9 PET studies were negative for active disease versus CT positive and 2 PET studies showed PD, CT was negative. PET alone showed 94.1% sensitivity and 94.6% specificity versus 97.2% and 63.5% for CT, 100% and 95.9% for PET/CT.In BSTS for the purpose of initial staging, ETR, short-term, or long-term restaging, FDG-PET is more accurate than CT. Combined PET/CT has higher accuracy than either alone.
Early high-dose rosuvastatin prevented contrast-induced acute kidney injury in non–ST-elevation ACS
Authors: Amber O. Molnar, Amit X. Garg
Journal: Annals of Internal Medicine (2014)

Source Citation Leoncini M, Toso A, Maioli M, et al. Early high-dose rosuvastatin for contrast-induced nephropathy prevention in acute coronary syndrome: results from the PRATO-ACS Study (Protective Effect of Rosuvastatin and Antiplatelet Therapy On Contrast-Induced Acute Kidney Injury and Myocardial Damage in Patients With Acute Coronary Syndrome). J Am Coll Cardiol. 2014;63:71-9. 24076283
Cardiac complications in relapsed and refractory multiple myeloma patients treated with carfilzomib
Authors: S Atrash, A Tullos, S Panozzo, M Bhutani, F Van Rhee, B Barlogie, S Z Usmani
Journal: Blood Cancer Journal (2015)

Carfilzomib is a novel, highly selective, tetrapeptide epoxyketone proteasome inhibitor that irreversibly binds to the N-terminal threonine-containing active sites of the 20S proteasome, which is the proteolytic core particle within the 26S proteasome, as compared with bortezomib, which reversibly inhibits the 20S proteasome. 1 In vitro, carfilzomib has demonstrated antiproliferative and proapoptotic activities in solid and hematologic tumor cells. 2 In animals, carfilzomib inhibited proteasome activity in blood and tissue and delayed tumor growth in models of multiple myeloma, hematologic and solid tumors. 1 Proteasome inhibition was maintained for ⩾ 48 h following the first dose of carfilzomib in each week of dosing. 1 In addition, carfilzomib administration resulted in the inhibition of the low-molecular mass polypeptide two and multicatalytic endopeptidase complex-like one subunit of the immunoproteasome ranging from 26 to 32% and 41 to 49%, respectively, at a dose of 20 mg/m 2 (ref. 3).5][6][7] In 2012, based on these results, carfilzomib was approved in the United States for single-agent use in the treatment of patients with MM who have received at least two prior therapies, including bortezomib and an immunomodulatory agent, and have demonstrated disease progression on or within 60 days of the completion of the last therapy. 8arfilzomib has the advantage of a favorable safety profilemost notably a low incidence of peripheral neuropathy, which is a common complication with bortezomib-based regimens.][11] An increasing body of evidence supports the assertion that deficient proteasome activity has a crucial role in the impairment of cardiac function.This effect may be mediated by several mechanisms, the most important of which is putatively the accumulation of unfolded, damaged and undegraded proteins inside myocytes. 11-13However, limited data are currently available on cardiac adverse events associated with carfilzomib treatment.Between 2009 and 2012, which was before regulatory approval of carfilzomib in the United States, we treated 130 patients with relapsed and/or refractory MM, either on a phase 2 compassionate carfilzomib protocol (n = 118) or as single-patient treatment with an investigational new drug (n = 12).We herein report data on those patients who developed a significant cardiovascular adverse event, which was defined as hospitalization owing to a cardiac complication during the first two cycles of therapy with carfilzomib either alone or with dexamethasone.Patients with hospitalization attributed to other causalities, such as infections, or who received concomitant anti-MM drugs were excluded from this analysis.We also describe subsets of patients with baseline echocardiogram findings from before and during carfilzomib treatment and with brain natriuretic peptide (BNP) measurements gathered at baseline and during follow-up.
Toxicity of azathioprine and monocrotaline in murine sinusoidal endothelial cells and hepatocytes: The role of glutathione and relevance to hepatic venoocclusive disease
Authors: L D DeLeve, X Wang, J F Kuhlenkamp, N Kaplowitz
Journal: Hepatology (1996)

The mechanisms leading to hepatic venoocclusive disease (HVOD) remain largely unknown. Azathioprine and monocrotaline were studied as part of a series of studies looking at a variety of toxins that induce HVOD to find common features that might be of pathogenic significance. In a previous study, dacarbazine showed selective in vitro toxicity to sinusoidal endothelial cells (SEC) compared with hepatocytes and a key role for SEC glutathione (GSH) was demonstrated. Murine SEC and hepatocytes were isolated and studied in culture. Azathioprine and monocrotaline were found to be selectively more toxic to SEC than to hepatocytes. The relative resistance of hepatocytes to azathioprine was due to enhanced GSH defense: hepatocytes exposed to azathioprine maintained intracellular GSH levels better than SEC, particularly when supplemental GSH precursors were added, and hepatocyte resistance was completely overcome by depletion of intracellular GSH. In contrast, monocrotaline toxicity in hepatocytes was largely unaffected by depletion of GSH, which suggests that selectivity of monocrotaline for SEC may be attributable to differences in metabolic activation. Both compounds are detoxified by GSH in SEC, as demonstrated by enhanced toxicity in the presence of buthionine sulfoximine (BSO) and attenuation of toxicity with exogenous GSH. SEC GSH levels were more than 70% to 80% depleted by monocrotaline and azathioprine, respectively, before cell death. Azathioprine and monocrotaline are selectively toxic to SEC; the mechanism of toxicity in the SEC may be caused by profound GSH depletion.
Characterization of Obstructive Nonapneic Respiratory Events in Moderate Sleep Apnea Syndrome
Authors: CLAIRE CRACOWSKI, JEAN-LOUIS PÉPIN, BERNARD WUYAM, PATRICK LÉVY
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Obstructive nonapneic respiratory events (ONAREs, i.e., obstructive hypopneas [OHs] and respiratory effort related arousals [RERAs]) are clinically important as producing sleep fragmentation but are much more difficult to detect and classify than obstructive apneas. We characterized 1,061 ONAREs in 15 unselected patients with moderate sleep apnea–hypopnea syndrome (OSAHS) according to the 1999 American Academy of Sleep Medicine (AASM) Task Force recommendations concerning accurate skills for respiratory measurements (i.e., pneumotachograph and esophageal pressure [Pes]) and definitions of respiratory events. OHs were defined as ⩾ 50% decrease in flow or < 50% but ⩾ 30% decrease in flow associated with either a desaturation of ⩾ 3% or a cortical arousal. RERAs corresponded to a less than 30% decrease in flow associated with an arousal. OHs represented a large majority of the events (79.9%, n = 848). Among the events demonstrating a 30 to 50% reduction in flow (n = 392), the occurrence of a cortical arousal permitted the classification of 246 events as OHs (62.8%). RERAs represented only 5.3% of the events. Finally 14.8% of the events were classified as indeterminate owing to a < 50% and ⩾ 30% airflow decrease without arousal or desaturation or an airflow decrease less than 30% without arousal. The same level of Δ Pes was observed at the end of OHs and RERAs (21.9 ± 5.5 versus 18.9 ± 5.7 cm H2O respectively [NS]) whereas the reduction in flow was as expected, higher for OH (57.9 ± 10.7 versus 21.3 ± 4.9%). In a population of moderate OSAHS, OH represented the dominant type of ONAREs when RERAs should be considered as specific but relatively rare respiratory events. The occurrence and the recognition of a microarousal represented the key associated factor for classifying respiratory events as hypopneas. The high rate (15%) of unclassified events demonstrated some limitations in the AASM Task Force recommendations for definitions of respiratory events. Similar levels of Δ Pes found at the end of RERAs and OHs, although the reduction in flow was higher for OHs, suggest that different levels of collapsibility can exist throughout the night in a given patient.
S66 A randomised crossover trial of pressure support ventilation (PSV) versus pressure controlled ventilation (PCV) in stable hypercapnic Chronic Obstructive Pulmonary Disease (COPD)
Authors: K. A. Brignall, P. B. Murphy, J. Moxham, M. Polkey, A. C. Davidson, N. Hart
Journal: Thorax (2010)

<h3>Introduction</h3> PSV, rather than PCV, is often the preferred mode of ventilatory support in stable hypercapnic COPD patients, although this is supported by limited data. We hypothesised that PCV would be equivalent to PSV with similar patient-ventilator synchrony, nocturnal ventilation, gas exchange and sleep quality with similar adherence to non-invasive ventilation and improvements in health related quality of life (HRQL). <h3>Method</h3> HypercapnicCOPD patients (daytime PaCO<sub>2</sub> &gt;6 kPa) were enrolled and randomised to PSV (low back up rate) or PCV for 6 weeks. Patients had baseline anthropometric, HRQL and gas exchange measurements, were re-assessed at 6 weeks and crossed over to the other arm with the final assessment at 12 weeks. Sleep quality was assessed using a sleep diary and nocturnal actigraphy (Actiwatch AW4, CamNTech, Cambridge, UK) for 2 weeks prior to each assessment. Subjective patient-ventilator synchrony was assessed with a questionnaire (Score 0–3, 0=good synchrony). At 6 and 12 weeks, all measurements were repeated, including ventilator adherence. <h3>Results</h3> 12 patients were enrolled. However, three were unable to tolerate NIV and 1 failed to adhere to the study protocol. Four commenced on PSV and 4 commenced on PCV. Mean (±SD) age 72±8 years, BMI 32±9 kg/m<sup>2</sup>, FEV<sub>1</sub>/FVC 54±14%, FEV<sub>1</sub> 29±11%, PaCO<sub>2</sub> 8.6±1.7 KPa and PaO<sub>2</sub> 7.3±1.4 KPa. Mean IPAP 28±4 cm H<sub>2</sub>O and mean EPAP 5±3 cm H<sub>2</sub>O. Backup rate for PSV was 6 bpm and PCV was 16±1 bpm. The mean nocturnal respiratory rate was 14±3 bpm and 16±1 bpm with triggering compliance of 90±9% and 24±10% for PSV and PCV, respectively. According to the patient-ventilator synchrony questionnaire, patients reported an increased awareness of ineffective efforts (0.7±0.5 vs 0.1±0.3; p=0.03) and a short inspiratory time (0.7±0.7 vs 0.1±0.3; p=0.03) during PSV, but there was no difference in self-reported sleep comfort and quality. Furthermore, there were no between group differences in change in PaCO<sub>2</sub>, ventilator use or nocturnal actigraphy. Although there were similar between group improvements in HRQL, the respiratory symptom domain of the Severe Respiratory Insufficiency Questionnaire favoured PSV (p=0.02). <h3>Conclusion</h3> Despite clinicians9 perception that PSV has an advantage over PCV for the management of patients with stable hypercapnic COPD, these pilot data do not necessarily support this view.