tbuckley/cabot-search huggingface dataset:
The nature of human serum insulin-like activity (ILA): characterization of ILA in serum and serum fractions obtained by acid-ethanol extraction and adsorption chromatography
Authors: Philip L. Poffenbarger, John W. Ensinck, Dieter K. Hepp, Robert H. Williams
Journal: Journal of Clinical Investigation (1968)

Studies were undertaken in an attempt to clarify the apparent heterogeneous nature of human serum insulin-like activity. Methods of preparative zone electrophoresis on Pevikon, acid-ethanol extraction of trichloroacetic acid serum protein precipitates, adsorption chromatography on DEAE-cellulose and Dowex 50, gel filtration chromatography, and insulin antiserum immunoreactivity were used. The results establish the presence of a substance in serum with in vitro biological properties similar to insuln but with different physicochemical properties. The major portion of serum ILA measured by bioassay techniques can be attributed to the effects of this substance. Whereas the in vitro biological effects of this substance on muscle and adipose cells were similar to those of crystalline insulin, the substance is distinguished from insulin by: (1) the failure of insulin antiserum to inhibit its in vitro biological effect; (2) a slower electrophoretic mobility (in the gamma-beta globulin zone); and (3) a larger molecular weight, between 40,000 and 50,000 in these studies. It is similar to insulin since both are soluble in acid-ethanol. The results further indicate that previously described insulin-like activity in gamma-beta globulin preparations, the major portion of total serum insulin activity described in acid-ethanol extracts of serum, "bound" insulin, "atypical" insulin, and antibody nonsuppressible insulin-like activity bioassayed in diluted serum are all one and the same substance.
Modulation of antigen processing by bound antibodies can boost or suppress class II major histocompatibility complex presentation of different T cell determinants.
Authors: P D Simitsek, D G Campbell, A Lanzavecchia, N Fairweather, C Watts
Journal: The Journal of Experimental Medicine (1995)

Bound antibodies can modulate antigen processing but it is not clear to what extent this affects antigen presentation. Here we show that presentation of T cell determinants in tetanus toxin can be either enhanced or suppressed as a direct consequence of antibody modulation of antigen processing in human B lymphoblastoid cells. Remarkably, a single bound antibody or its Fab fragment can simultaneously enhance the presentation of one T cell determinant by more than 10-fold while strongly suppressing the presentation of a different T cell determinant. Biochemical analysis demonstrates that both the suppressed and boosted determinants fall within an extended domain of antigen stabilized or "footprinted" by this antibody during proteolysis. These results demonstrate that bound antibodies can modulate the capture of peptides by class II major histocompatibility complex (MHC), thus manipulating the T cell response towards or away from particular determinants. Altered processing of protein-protein complexes leading to enhanced loading of class II MHC and substantially lowered threshold for T cell activation suggests a novel mechanism that might reveal "cryptic" self determinants.
Response to Comment on Kramer et al. Glucagon Response to Oral Glucose Challenge in Type 1 Diabetes: Lack of Impact of Euglycemia. Diabetes Care 2014;37:1076–1082
Authors: Caroline K. Kramer, Ravi Retnakaran, Bernard Zinman
Journal: Diabetes Care (2014)

We thank Ali et al. (1) for their comments on our article (2). In this study, we evaluated the impact of euglycemia versus hyperglycemia on the glucagon response to an oral glucose tolerance test (OGTT) in 10 participants with type 1 diabetes and showed that these patients have a paradoxical increase in glucagon in response to oral glucose that is not reversed when euglycemia is achieved prior to the test. This conclusion was based on assessment of glucagon response to the OGTT by five diverse statistical approaches, of which only one suggested a differential response under …
Effect of duration of ventricular fibrillation on defibrillation efficacy in humans.
Authors: R A Winkle, R H Mead, M A Ruder, N A Smith, W S Buch, V A Gaudiani
Journal: Circulation (1990)

The currently available automatic implantable cardioverter-defibrillator has proven highly successful for termination of ventricular tachycardia and fibrillation. Newer devices, however, permit lower energy shocks to be delivered initially and longer episodes of arrhythmia to occur before shocks are delivered. These changes may result in longer durations of arrhythmia before successful termination. Little is known about the effects of the duration of ventricular fibrillation on the efficacy of defibrillating shocks. In this study, we examined the efficacy of defibrillating shocks in 22 patients undergoing automatic implantable cardioverter-defibrillator implantation or generator change. Defibrillating shocks ranging from 300 to 600 V (5.9-24.2 J) were delivered in matched pairs after 5 and 15 seconds of ventricular fibrillation. For the 300-V shocks (5.9 J), defibrillation was accomplished in 82% of patients when the shocks were given after 5 seconds of ventricular fibrillation and in only 45% of patients when the shocks were delivered after 15 seconds (p less than 0.01). At higher energies, there was no difference in the efficacy of defibrillation shocks delivered after 5 compared with 15 seconds of ventricular fibrillation. The postshock aortic, systolic, and diastolic blood pressures were significantly lower when the shocks were given after 15 seconds of ventricular fibrillation than after only 5 seconds. We conclude that the duration of ventricular fibrillation affects defibrillation efficacy especially at energies that are relatively low compared with maximal device outputs and that longer episodes of ventricular fibrillation cause more postshock hemodynamic depression. These observations have implications for defibrillation threshold testing at the time of device implantation and for the design and programming of future automatic implantable antitachycardia devices.
DERMATITIS CAUSED BY RECURRENT URINARY INFECTION.
Authors: SUZANNE ALEXANDER, H. R. VICKERS
Journal: British Journal of Dermatology (1962)

Journal Article DERMATITIS CAUSED BY RECURRENT URINARY INFECTION. Get access SUZANNE ALEXANDER, SUZANNE ALEXANDER Department of Dermatology, The Radcliffe Infirmary, Oxford Search for other works by this author on: Oxford Academic Google Scholar H. R. VICKERS H. R. VICKERS Department of Dermatology, The Radcliffe Infirmary, Oxford Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 74, Issue 8-9, 1 August 1962, Pages 307–309, https://doi.org/10.1111/j.1365-2133.1962.tb13516.x Published: 01 August 1962
Association of the transfer coefficient of the lung for carbon monoxide with emphysema progression in male smokers
Authors: F.A.A. Mohamed Hoesein, P. Zanen, B. van Ginneken, R.J. van Klaveren, J-W.J. Lammers
Journal: European Respiratory Journal (2011)

A decreased transfer coefficient of the lung for carbon monoxide (K(CO)) is associated with emphysema. We evaluated whether in heavy smokers, baseline K(CO) was associated with the progression of computed tomography (CT)-detected emphysema, and the progression of airflow limitation. Heavy smokers, mean ± sd 41.3 ± 18.7 pack-yrs, participating in a lung cancer screening trial underwent diffusion testing and CT scanning of the lungs. CT scanning was repeated after median (25th-75th percentile) 2.8 (2.7-3.0) yrs and emphysema was assessed by lung densitometry using the 15th percentile. The association between K(CO) at baseline with progression of emphysema and lung function decline was assessed by multiple linear regression, correcting for baseline CT-quantified emphysema severity and forced expiratory volume in 1 s (FEV₁/forced vital capacity (FVC), age, height, body mass index, pack-yrs and smoking status (current or former smoker). 522 participants aged 60.1 ± 5.4 yrs were included. Mean ± sd 15th percentile was -938 ± 19, absolute FEV₁/FVC was 71.6 ± 9% and K(CO) was 1.23 ± 0.25, which is 81.8 ± 16.5% of predicted. By interpolation, a one sd (0.25) lower K(CO) value at baseline predicted a 1.6 HU lower 15th percentile and a 0.78% lower FEV₁/FVC after follow-up (p < 0.001). A lower baseline K(CO) value is independently associated with a more rapid progression of emphysema and airflow limitation in heavy smokers.
SOME ASPECTS OF THE LEGAL RESPONSIBILITY OF MEDICAL MEN
Authors: A. D. Cowburn
Journal: BMJ (1909)

HISTORICAL.FROM the earliest times of which we have any authentic records, the responsibilities, liabilities, and privileges of medical men have been the subject of legislation.Yet the measure of that responsibility has varied greatly in times past, and amongst divers nations.The oldest known Code of Laws, promulgated by Hammurabi, King of Babylon, during the period 2285-2242 B.c., and which is believed by scholars of Assyriology to embody the best judicial decisions prior to that period, enacted the privileges, fees, and serious liabilities of those venturesome enough to practise medicine and surgery.After laying down a scale of fees which then, as now, varied with the social status of the patient, the code proceeds:If the doctor has treated a gentleman for a severe wound with a lancet of bronze, and has caused the gentleman to die, or has opened an abscess of the eye for a gentleman with a bronze lancet, and has caused the loss of the gentleman's eye, one shall cut off his hands.If a doctor has treated the severe wound of a slave of a poor man, and has caused his death, he shall render slave for slave.If he has opened his abscess with a bronze lancet, and has made him lose his eye, he shall pay money, half his price.
A Phase 1 Pharmacokinetic and Pharmacodynamic Study of the Histone Deacetylase Inhibitor Belinostat in Patients with Advanced Solid Tumors
Authors: Nicola L. Steele, Jane A. Plumb, Laura Vidal, Jette Tjørnelund, Poul Knoblauch, Annie Rasmussen, Chean Eng Ooi, Peter Buhl-Jensen, Robert Brown, T.R. Jeffry Evans, Johann S. DeBono
Journal: Clinical Cancer Research (2008)

Abstract Purpose: To determine the safety, dose-limiting toxicity, maximum tolerated dose, and pharmacokinetic and pharmacodynamic profiles of the novel hydroxamate histone deacetylase inhibitor belinostat (previously named PXD101) in patients with advanced refractory solid tumors. Experimental Design: Sequential dose-escalating cohorts of three to six patients received belinostat administered as a 30-min i.v. infusion on days 1 to 5 of a 21-day cycle. Pharmacokinetic variables were evaluated at all dose levels. Pharmacodynamic measurements included acetylation of histones extracted from peripheral blood mononuclear cells, caspase-dependent cleavage of cytokeratin-18, and interleukin-6 levels. Results: Forty-six patients received belinostat at one of six dose levels (150-1,200 mg/m2/d). Dose-limiting toxicities were grade 3 fatigue (one patient at 600 mg/m2; one patient at 1,200 mg/m2), grade 3 diarrhea combined with fatigue (one patient at 1,200 mg/m2), grade 3 atrial fibrillation (one patient at 1,200 mg/m2; one patient at 1,000 mg/m2), and grade 2 nausea/vomiting leading to inability to complete a full 5-day cycle (two patients at 1,000 mg/m2). The maximum tolerated dose was 1,000 mg/m2/d. I.v. belinostat displayed linear pharmacokinetics with respect to Cmax and AUC. The intermediate elimination half-life was 0.3 to 1.3 h and was independent of dose. Histone H4 hyperacetylation was observed after each infusion and was sustained for 4 to 24 h in a dose-dependent manner. Increases in interleukin-6 levels were detected following belinostat treatment. Stable disease was observed in a total of 18 (39%) patients, including 15 treated for ≥4 cycles, and this was associated with caspase-dependent cleavage of cytokeratin-18. Of the 24 patients treated at the maximum tolerated dose (1,000 mg/m2/d), 50% achieved stable disease. Conclusions: I.v. belinostat is well tolerated, exhibits dose-dependent pharmacodynamic effects, and has promising antitumor activity.
TWO METHODS OF CALCULATING ANKLE BRACHIAL INDEX: DIFFERENCES IN PREDICTING PERIPHERAL ARTERIAL DISEASE BURDEN
Authors: Bassem M. Chehab, Vinodh Jeevanantham, Sravanthi Nagavalli, Edgar Austria, Rakesh Shrivastava, Mark Wiley, Peter Tadros, Jayant Nath, Buddhadeb Dawn, Kamal Gupta
Journal: Journal of the American College of Cardiology (2012)
Potential and Actual Neonatal Organ and Tissue Donation After Circulatory Determination of Death
Authors: Justin Stiers, Cecile Aguayo, Angela Siatta, Angela P. Presson, Richard Perez, Robert DiGeronimo
Journal: JAMA Pediatrics (2015)

The need for transplants continues to exceed organ and tissue donor availability. Although recent surgical advances have resulted in successful transplants using very small pediatric donors, including neonates, the actual practice of neonatal organ donation after circulatory determination of death (DCDD) remains uncommon.To describe the percentage of neonates potentially eligible for DCDD, including those who underwent successful donation, and reasons for ineligibility in those who did not in a single neonatal intensive care unit (NICU).We obtained data from the Children's Hospital Neonatal Database and Intermountain Donor Services (IDS) organ procurement records. The 136 deaths that occurred in the NICU of the Primary Children's Hospital, Salt Lake City, Utah, from January 1, 2010, through May 7, 2013, were reviewed retrospectively from January 12 through July 1, 2014, to determine potential eligibility for DCDD as determined by IDS minimum eligibility criteria (requirement of life-sustaining interventions and weight >2 kg). For patients who did not undergo DCDD, we reviewed records to determine the reasons for ineligibility.Potential eligibility for DCDD among neonates who died in the study NICU.Of 136 deaths in the NICU, 60 (44.1%) met criteria for DCDD; however, fewer than 10% were referred appropriately to the regional organ procurement organization for evaluation. Forty-five neonates (33.1%) ultimately died within 90 minutes of withdrawal of life-sustaining interventions and thus would have been eligible for organ donation based on warm ischemic time. The most common causes of death among the 60 potentially eligible neonatal donors were neonatal encephalopathy (n = 17) and multiple congenital anomalies (n = 14). Nonreferral or late referral by the medical team was the most frequent reason for donor ineligibility, including 49 neonates (36.0%). Overall, only 4 neonates (2.9%) underwent successful DCDD.Although almost half of all neonatal deaths identified met minimum IDS criteria, most of these patients were not referred or were referred too late for evaluation. Although small size remains the primary reason for exclusion from DCDD, improved education with regard to criteria and the importance of timely referral by neonatologists and other members of the NICU team would likely result in a significant increase of future donations.
Final Report of the Intergroup Randomized Study of Combined Androgen-Deprivation Therapy Plus Radiotherapy Versus Androgen-Deprivation Therapy Alone in Locally Advanced Prostate Cancer
Authors: Malcolm D. Mason, Wendy R. Parulekar, Matthew R. Sydes, Michael Brundage, Peter Kirkbride, Mary Gospodarowicz, Richard Cowan, Edmund C. Kostashuk, John Anderson, Gregory Swanson, Mahesh K.B. Parmar, Charles Hayter, Gordana Jovic, Andrea Hiltz, John Hetherington, Jinka Sathya, James B.P. Barber, Michael McKenzie, Salah El-Sharkawi, Luis Souhami, P.D. John Hardman, Bingshu E. Chen, Padraig Warde
Journal: Journal of Clinical Oncology (2015)

Purpose We have previously reported that radiotherapy (RT) added to androgen-deprivation therapy (ADT) improves survival in men with locally advanced prostate cancer. Here, we report the prespecified final analysis of this randomized trial. Patients and Methods NCIC Clinical Trials Group PR.3/Medical Research Council PR07/Intergroup T94-0110 was a randomized controlled trial of patients with locally advanced prostate cancer. Patients with T3-4, N0/Nx, M0 prostate cancer or T1-2 disease with either prostate-specific antigen (PSA) of more than 40 μg/L or PSA of 20 to 40 μg/L plus Gleason score of 8 to 10 were randomly assigned to lifelong ADT alone or to ADT+RT. The RT dose was 64 to 69 Gy in 35 to 39 fractions to the prostate and pelvis or prostate alone. Overall survival was compared using a log-rank test stratified for prespecified variables. Results One thousand two hundred five patients were randomly assigned between 1995 and 2005, 602 to ADT alone and 603 to ADT+RT. At a median follow-up time of 8 years, 465 patients had died, including 199 patients from prostate cancer. Overall survival was significantly improved in the patients allocated to ADT+RT (hazard ratio [HR], 0.70; 95% CI, 0.57 to 0.85; P &lt; .001). Deaths from prostate cancer were significantly reduced by the addition of RT to ADT (HR, 0.46; 95% CI, 0.34 to 0.61; P &lt; .001). Patients on ADT+RT reported a higher frequency of adverse events related to bowel toxicity, but only two of 589 patients had grade 3 or greater diarrhea at 24 months after RT. Conclusion This analysis demonstrates that the previously reported benefit in survival is maintained at a median follow-up of 8 years and firmly establishes the role of RT in the treatment of men with locally advanced prostate cancer.
IRRESPONSIBILITY OF JUVENILE DELINQUENTS
Authors: D. A. THOM
Journal: American Journal of Psychiatry (1942)

1. The constitutional psychopath or the psychopathic personality represents the most difficult group of all the mentally sick individuals with which the medical and legal professions have to deal. Particularly baffling are those psychopaths who show evidences of perversions in relation to their sexual drives. 2. The psychiatrist is in a position to recognize in many instances during the preadolescence years definite tendencies for these unstable children to incorporate into the framework of their disintegrated personalities sexual anomalies which are significant and have grave implications. We recognize that such individuals are not governed by the same inhibiting forces as the normal individual. They are impulsive, cunning, and unpredictable. They have no regrets, remorse, or sense of guilt about their asocial activities. They do not profit from experience, they are not restrained by punishment, and up to the present time they do not improve under treatment. 3. The case presented is an example of the personality type which is in need of serious consideration from both the medical and legal professions. 4. There seem to be two vitally important points which have not, as yet, been given sufficient consideration by those interested in psychiatry and criminology. (a) A statute should be enacted which would permit or require the court to have those suspected of sexual psychopathy submitted to psychiatric examination by two qualified psychiatrists in order to determine their responsibility. If the evidence of this examination is of such a nature as to convince the court of their irresponsibility because of sexual psychopathy they should be sent to an institution providing care for this type of individual. (b) The fact that no such institution exists at the present time brings up the need of providing an institution so organized that a thorough study might be made from every possible angle, medical, psychological, psychiatric. Let us turn our battery of tests on these individuals, study their behavior under strict supervision or modified supervision, but always supervision, until we have some assurance that they will not return to society only to repeat more serious offenses.
Nocturnal assisted ventilation using bilevel positive airway pressure: the effect of expiratory positive airway pressure
Authors: MW Elliott, AK Simonds
Journal: European Respiratory Journal (1995)

Increasing expiratory positive airway pressure (EPAP) has theoretical advantages during overnight nasal ventilation. We wanted to evaluate the effect of the addition of EPAP upon the control of nocturnal hypoventilation. Seven patients with neuromuscular/skeletal (NMS) disorder (mean +/- SD forced vital capacity (FVC) 1.06 +/- 0.28 l, arterial oxygen tension (PaO2) 9.1 +/- 0.6 kPa, and arterial carbon dioxide tension (PaCO2) 6.9 +/- 0.9 kPa), and seven patients with chronic obstructive pulmonary disease (COPD) (FEV1 0.46 +/- 0.14 l, PaO2 6.2 +/- 0.6 kPa, and PaCO2 8.4 +/- 1.1 kPa) all underwent full polysomnography on two nights during bilevel positive airway pressure (BiPAP) ventilation, with and without the addition of expiratory positive airway pressure, which was matched to the level of dynamic positive end-expiratory pressure (PEEP) or set at a minimum value of 5 cmH2O. In the group with neuromuscular/skeletal disorders the maximum transcutaneous carbon dioxide tension (PtcCO2) overnight was lower (inspiratory positive airway pressure (IPAP) 8.1 +/- 1.4 kPa, IPAP/EPAP 7.3 +/- 0.9 kPa) and the minimum level of arterial oxygen saturation (SaO2 min) increased (IPAP 77.1 +/- 6.7%, IPAP/EPAP 83.6 +/- 4.2%) when expiratory positive airway pressure was added. There were no differences in mean PtcCO2 or mean oxygen saturation, but sleep quality was worse (non-rapid eye movement (non-REM) sleep IPAP 266 +/- 44 min, IPAP/EPAP 226 +/- 32 min). In the patients with COPD, expiratory positive airway pressure conferred no advantage.(ABSTRACT TRUNCATED AT 250 WORDS)
Connexin Gene Transfer Preserves Conduction Velocity and Prevents Atrial Fibrillation
Authors: Tomonori Igarashi, J. Emanuel Finet, Ayano Takeuchi, Yoshihisa Fujino, Maria Strom, Ian D. Greener, David S. Rosenbaum, J. Kevin Donahue
Journal: Circulation (2011)

Several lines of evidence have suggested that maintenance of atrial fibrillation (AF) depends on reentrant mechanisms. Maintenance of reentry necessitates a sufficiently short refractory period and/or delayed conduction, and AF has been associated with both alterations. Fibrosis, cellular dysfunction, and gap junction protein alterations occur in AF and cause conduction delay. We performed this study to test the hypothesis that gap junction protein overexpression would improve conduction and prevent AF.Thirty Yorkshire swine were randomized into 2 groups (sinus rhythm and AF), and each group into 3 subgroups: sham-operated control, gene therapy with adenovirus expressing connexin (Cx) 40, and gene therapy with adenovirus expressing Cx43 (n=5 per subgroup). All animals had epicardial gene painting; the AF group had burst atrial pacing. All animals underwent terminal study 7 days after gene transfer. Sinus rhythm animals had strong transgene expression but no atrial conduction changes. In AF animals, controls had reduced and lateralized Cx43 expression, and Cx43 gene transfer restored expression and cellular location to sinus rhythm control levels. In the AF group, both Cx40 and Cx43 gene transfer improved conduction and reduced AF relative to controls.Connexin gene therapy preserved atrial conduction and prevented AF.