tbuckley/cabot-search huggingface dataset:
Inhibition of<i>in vivo</i>rat liver regeneration by 2-acetylaminofluorene affects the regulation of cell cycle-related proteins
Authors: Lena C. E. Ohlson, Lena Koroxenidou, Inger Porsch Hällström
Journal: Hepatology (1998)

The effects of dietary 2-acetylaminofluorene (2-AAF) on cell cycle-related proteins was studied in regenerating livers from male Wistar rats. The levels of cyclins, cyclin dependent kinases (cdks), and related proteins were studied at different times during the first cell cycle after partial hepatectomy (PH). The frequency of proliferation cell nuclear antigen (PCNA)-positive nuclei, a marker of S phase progression, was almost zero during the first 27 hours after PH in the mitoinhibited 2-AAF-treated rats, while about 50% of the nuclei were labeled 24 hours after PH in control animals. Accordingly, Western blot tests showed markedly elevated PCNA protein levels from 18 hours to the end of S phase in untreated animals but no upregulation in response to 2-AAF. Compared with control animals, animals treated with 2-AAF showed increased levels of cdk 4 and cyclin D 3 from 12 and 15 hours after PH, respectively, and altered cyclicity in cyclin D 3 expression. No effects on cyclin E were observed, while the increase in cdk 2 levels in control animals during late G 1 /S (15-27 hours) was abolished by 2-AAF. p53 was induced by 2-AAF treatment during the same period, with a peak at 24 hours. The protein detected with p21 antibodies was highly expressed in unstimulated hepatocytes in control animals, and further increased by 2-AAF. The expression was sustained until 15 hours after PH in control rats while 2-AAF-treated animals lacked detectable protein during this period; however, a transient increase was observed at 21 hours. Thus, 2-AAF affects several parameters of cell cycle regulation of possible relevance for its inhibitory effects on hepatocyte proliferation in vivo.
The Doctor and His Dictionary
Authors: Ruth Good
Journal: New England Journal of Medicine (1966)

PARADOXICALLY, a physician can get help from a dictionary only in proportion to his own understanding of lexicography, knowledge of language, and sensitivity toward usage. The dictionary's ground rules show him how its vocabulary is arranged, but his personal tastes and experiences govern his specific selection from that linguistic smorgasbord.Another paradox is that when the physician "takes from" the source of language he also "gives to" its substance and variety. Medical language is formed by the people who use it, and the shape it takes reflects their scholarship and largely governs what goes into the dictionary. In other words, . . .
Intraductal Ultrasound for the Evaluation of Patients with Biliary Strictures and No Abdominal Mass on Computed Tomography
Authors: S. Stavropoulos, A. Larghi, E. Verna, P. Battezzati, P. Stevens
Journal: Endoscopy (2005)

Endoscopic retrograde cholangiopancreatography (ERCP) is the diagnostic procedure of choice in patients with biliary strictures and no culprit mass lesion on abdominal imaging, but it is limited in its diagnostic accuracy. The aim of this prospective study was to determine the value of intraductal ultrasound (IDUS) in distinguishing between benign and malignant biliary strictures in this clinical setting.Sixty-one patients with painless jaundice and no mass lesion on abdominal computed tomography, who were found to have a biliary stricture at ERCP, underwent IDUS with a high-frequency (20-MHz) wire-guided probe. Histopathological confirmation or clinical follow-up was used to establish the final diagnosis. The diagnostic performances of IDUS, ERCP, and IDUS plus ERCP in the identification of malignant strictures were evaluated.Forty-three patients had malignant strictures and 18 had benign strictures. ERCP produced 25 false-negative diagnoses, 22 of which were identified as malignant by IDUS. IDUS provided seven false-negative and three false-positive diagnoses. The proportion of patients with malignant strictures who tested positive with IDUS was 2.06 times that of ERCP (95 % CI, 1.37 - 3.10; 83.3 % vs. 40.5 %, P = 0.0004). When used in conjunction, IDUS increased the accuracy of ERCP from 58 % to 90 %. Patients with operable lesions on IDUS and no contraindication to surgery underwent resection; most patients with pancreatic parenchymal invasion on IDUS underwent EUS, which identified a pancreatic mass in more than 50 % of cases. Patients with negative IDUS and a low clinical suspicion for malignancy were treated endoscopically, while a more aggressive work-up was performed in all patients with high pretest probability, regardless of the IDUS results.IDUS is a valuable adjunct to ERCP in the characterization of biliary strictures in patients who present with painless jaundice in the absence of a culprit mass on abdominal imaging.
Effect of Sensor-Augmented Insulin Pump Therapy and Automated Insulin Suspension vs Standard Insulin Pump Therapy on Hypoglycemia in Patients With Type 1 Diabetes
Authors: Trang T. Ly, Jennifer A. Nicholas, Adam Retterath, Ee Mun Lim, Elizabeth A. Davis, Timothy W. Jones
Journal: JAMA (2013)

Hypoglycemia is a critical obstacle to the care of patients with type 1 diabetes. Sensor-augmented insulin pump with automated low-glucose insulin suspension has the potential to reduce the incidence of major hypoglycemic events.To determine the incidence of severe and moderate hypoglycemia with sensor-augmented pump with low-glucose suspension compared with standard insulin pump therapy.A randomized clinical trial involving 95 patients with type 1 diabetes, recruited from December 2009 to January 2012 in Australia.Patients were randomized to insulin pump only or automated insulin suspension for 6 months.The primary outcome was the combined incidence of severe (hypoglycemic seizure or coma) and moderate hypoglycemia (an event requiring assistance for treatment). In a subgroup, counterregulatory hormone responses to hypoglycemia were assessed using the hypoglycemic clamp technique.Of the 95 patients randomized, 49 were assigned to the standard-pump (pump-only) therapy and 46 to the low-glucose suspension group. The mean (SD) age was 18.6 (11.8) years; duration of diabetes, 11.0 (8.9) years; and duration of pump therapy, 4.1 (3.4) years. The baseline rate of severe and moderate hypoglycemic events in the pump-only group was 20.7 vs 129.6 events per 100 patient months in the low-glucose suspension group. After 6 months of treatment, the event rates decreased from 28 to 16 in the pump-only group vs 175 to 35 in the low-glucose suspension group. The adjusted incidence rate per 100 patient-months was 34.2 (95% CI, 22.0-53.3) for the pump-only group vs 9.5 (95% CI, 5.2-17.4) for the low-glucose suspension group. The incidence rate ratio was 3.6 (95% CI, 1.7-7.5; P <.001). There was no change in glycated hemoglobin in either group: mean, 7.4 (95% CI, 7.2-7.6) to 7.4 (95% CI, 7.2-7.7) in the pump-only group vs mean, 7.6 (95%, CI, 7.4-7.9) to 7.5 (95% CI, 7.3-7.7) in the low-glucose suspension group. Counterregulatory hormone responses to hypoglycemia were not changed. There were no episodes of diabetic ketoacidosis or hyperglycemia with ketosis.Sensor-augmented pump therapy with automated insulin suspension reduced the combined rate of severe and moderate hypoglycemia in patients with type 1 diabetes.anzctr.org.au Identifier: ACTRN12610000024044.
The Bradshaw Lecture ON PROGNOSIS IN RELATION TO TREATMENT OF TUBERCULOSIS OF THE GENITOURINARY ORGANS: Delivered before the Royal College of Surgeons of England
Authors: R. J. Godlee
Journal: BMJ (1907)

THE Pious FOUNDER.THE simplest method of securing a limited immortality is that which involves the periodical mention of the name of a beneficiary by speakers or lecturers.As long as the DEc., i4, 1907.]172~TBRUOI FGNT-URNR ORAS DC 4 g 1.That it is usually a chronic disease, and that a majority of those cases which appear to be acute or sub- acute have been preceded by a slow enlargement of the organ which has escaped the attention of the patient.And this is based upon the facts that thicken- ings of the epididymis are often discovered acci- dentally, and that, in operations on the acute or subacute cases, more extensive cheesy masses are
Impact of IL28B on treatment outcome in hepatitis C virus G1/4 patients receiving response-guided therapy with peginterferon alpha-2a (40KD)/ribavirin
Authors: Thomas-Matthias Scherzer, Albert Friedrich Stättermayer, Michael Strasser, Hermann Laferl, Andreas Maieron, Rudolf Stauber, Christian Datz, Emina Dulic-Lakovic, Petra Steindl-Munda, Harald Hofer, Peter Ferenci
Journal: Hepatology (2011)

The IL28B genotype is the most important pretreatment predictor of treatment outcome in patients with chronic hepatitis C. The impact of the rs12979860 genotype on relapse was retrospectively evaluated in genotype 1/4 patients who received response-guided therapy with peginterferon alpha-2a 180 μg/week plus ribavirin 1,000/1,200 mg/day in a large, randomized, multicenter study. Patients with a rapid virologic response (RVR: hepatitis C virus [HCV] RNA <50 IU/mL) at week 4 were treated for 24 weeks; those with a slow virologic response (no RVR but undetectable HCV RNA or ≥ 2-log(10) decrease at week 12) were randomized to 48 (group A) or 72 weeks of treatment (group B). Relapse rates were compared by rs12979860 genotype (C/C versus combined T/C or T/T [T/*]) in patients with confirmed end-of-treatment response and known end-of-follow-up status (sustained virologic response [SVR] or relapse). The rs12979860 genotype was determined for 340/551 study participants. In patients with RVR and C/C or T/* genotype, relapse rates were similar (10.7% versus 15.2%). In patients randomized to groups A and B, relapse rates were similar in patients with C/C genotype randomized to group A (26.9%) and group B (20.0%). In contrast, relapse rates in T/* patients differed markedly between groups A and B, overall (42.9% and 18.8%; P < 0.025, respectively) and in those with low (<400,000 IU/mL: 37.5% versus 18.8%) and high (≥ 400,000 IU/mL: 45.0% versus 18.8%) baseline viral loads.The results suggest that the benefits of extended therapy are restricted to patients with a T allele. Relapse rates are highest in patients with T/* genotype and are markedly higher in slow responders treated for 48 weeks compared with 72 weeks.
HLA-C and Killer Cell Immunoglobulin-like Receptor Genes in Idiopathic Bronchiectasis
Authors: Rosemary J. Boyton, John Smith, Rosemary Ward, Meinir Jones, Lorraine Ozerovitch, Robert Wilson, Marlene Rose, John Trowsdale, Daniel M. Altmann
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

In idiopathic bronchiectasis, lung inflammation and chronic bacterial infection lead to progressive lung damage. A possible role for natural killer (NK) cells is suggested by the observation that familial bronchiectasis occurs in a rare group of individuals with impaired HLA class I expression and consequent NK cell dysfunction.Because the HLA-C locus and killer cell immunoglobulin-like receptors (KIRs) are of key importance for NK cell recognition, we analyzed HLA-C/KIR combinations by genotyping patients with idiopathic bronchiectasis.Genomic DNA from 96 individuals with idiopathic bronchiectasis and 101 control subjects was analyzed by polymerase chain reaction with sequence-specific primers. High-resolution HLA-C genotyping was performed in addition to KIR analysis.HLA-Cw*03 alleles and, in particular, HLA-C group 1 homozygosity are associated with the presence of bronchiectasis. Analysis of the relationship between HLA-C and KIR genes suggests a shift to activatory NK cell function.This is the first demonstration of genetic susceptibility in idiopathic bronchiectasis. The association with HLA-C group 1 homozygosity, and the interplay between HLA-C and KIR genes, argue for a role for NK cells in the progressive lung damage seen in this disease. This will require further investigation using functional studies.
Facial flushing after intra-articular injection of steroid.
Authors: M Pattrick, M Doherty
Journal: BMJ (1987)

Our findings are in direct contrast with those of Dundee et al.2A much larger study, of more than 200 subjects, would be required to rule out even a minor antiemetic effect of acupuncture (that is, a 10% difference between the groups).We chose, however, to limit our study to 46 subjects, as our results suggested that acupuncture at the P6 locus, in the way that we used it, is unlikely to be a clinically useful prophylactic for postoperative nausea and vomiting.
Effects of influx of holidaymakers on an acute medical unit in Cornwall.
Authors: S D Horsley, P J Smail, A K Thould
Journal: BMJ (1975)

This paper illustrates the effect of a large influx of holidaymakers on a medical unit in Cornwall. Increasing numbers of visitors are coming to Cornwall and, unless adequate resources are allocated for their efficient medical care, the medical facilities available to the residents will suffer greatly.
Crowdfunding sought for study that will provide first images of human brain on LSD
Authors: I. Torjesen
Journal: BMJ (2015)

The neuropsychopharmacologist who was sacked as the UK government’s adviser on drugs after he argued against tougher laws on cannabis and ecstasy is trying to raise crowdfunding to support research into the effects of LSD on the brain.

Numerous studies were conducted on LSD in the 1950s and 1960s, but there have been only three in the 50 years since the drug was made illegal in 1967, and none in the United Kingdom, because of the difficulty and cost of getting the necessary licences to undertake the research.

David Nutt, professor of …
Re-entrant ventricular arrhythmias in the late myocardial infarction period. 1. Conduction characteristics in the infarction zone.
Authors: N El-Sherif, B J Scherlag, R Lazzara, R R Hope
Journal: Circulation (1977)

Dogs 3-7 days following ligation of the anterior descending coronary artery representing a remarkably stable model for re-entrant ventricular arrhythmias (RVA) and allowed detailed electrophysiologic studies of the re-entrant mechanism. In these dogs, we could regularly illustrate the presence of continuous electrical activity originating from the infarction zone (IZ) and bridging the diastolic interval between the initiating and re-entrant beats as well as between consecutive re-entrant beats. Conduction in the IZ was highly complex, with multiple potentially re-entrant pathways, functionally dissociated areas, and areas of localized ventricular fibrillation. Conduction disorders in ischemic myocardium were consistently tachycardia-dependent with the spontaneous onset of RVA specifically associated with a Wenckebach-like conduction pattern in a potentially re-entrant pathway. Both manifest and concealed re-entry, as well as re-entrant beats with regular extrasystolic grouping, constant or variable coupling, uniform multiform and bidirectional QRS configurations, were related to characteristic conduction patterns in the IZ. In summary, the study provides the first direct in vivo evidence of ventricular re-entry and demonstrates propensity for RVA and sudden death in the late myocardial infarction period.
Cost-effectiveness of Incorporating Inactivated Poliovirus Vaccine Into the Routine Childhood Immunization Schedule
Authors: Mark A. Miller
Journal: JAMA (1996)

<h3>Objective.</h3> —To evaluate the economic consequences of introducing inactivated poliovirus vaccine (IPV) into the routine vaccination schedule in the United States to reduce vaccine-associated paralytic poliomyelitis (VAPP). <h3>Design.</h3> —Cost-benefit and cost-effectiveness models were formulated to compare the current national 4-dose live attenuated oral poliovirus vaccine (OPV) schedule with a 4-dose IPV schedule or a sequential schedule of 2 doses of IPV followed by 2 doses of OPV. Model assumptions were derived from the National Health Interview Survey (1994), current prices for OPV and IPV, a Delphi panel, compensatory awards by the National Vaccine Injury Compensation Program, and published and unpublished reports. <h3>Main Outcome Measures.</h3> —Annual societal incremental cost relative to the current schedule for the cost-benefit model; cost per VAPP case prevented for the cost-effectiveness model. <h3>Results.</h3> —Changing to an IPV-only or a sequential schedule would cost $28.1 million and $14.7 million, respectively. The costs per case of VAPP prevented were estimated as $3.0 million and $3.1 million for each option, respectively. Outcomes were most sensitive to the number of additional visits that may occur to avoid multiple injections. <h3>Conclusions.</h3> —The introduction of IPV into the routine vaccination schedule would not be cost-beneficial at current vaccine prices and with the current compensation awards paid to VAPP cases. The analysis provides a range of costs that policymakers need to consider if they wish to prevent VAPP. Although these costs are higher than those of other public health prevention programs, they may be justified because VAPP continues to occur as a result of government-mandated vaccination policies in the absence of known wild poliovirus transmission in the United States.
Short-Term Changes in Respiratory Biomarkers after Swimming in a Chlorinated Pool
Authors: Laia Font-Ribera, Manolis Kogevinas, Jan-Paul Zock, Federico P. Gómez, Esther Barreiro, Mark J. Nieuwenhuijsen, Pilar Fernandez, Carolina Lourencetti, Maitane Pérez-Olabarría, Mariona Bustamante, Ricard Marcos, Joan O. Grimalt, Cristina M. Villanueva
Journal: Environmental Health Perspectives (2010)

Swimming in chlorinated pools involves exposure to disinfection by-products (DBPs) and has been associated with impaired respiratory health.We evaluated short-term changes in several respiratory biomarkers to explore mechanisms of potential lung damage related to swimming pool exposure.We measured lung function and biomarkers of airway inflammation [fractional exhaled nitric oxide (FeNO), eight cytokines, and vascular endothelial growth factor (VEGF) in exhaled breath condensate], oxidative stress (8-isoprostane in exhaled breath condensate), and lung permeability [surfactant protein D (SP-D) and the Clara cell secretory protein (CC16) in serum] in 48 healthy nonsmoking adults before and after they swam for 40 min in a chlorinated indoor swimming pool. We measured trihalomethanes in exhaled breath as a marker of individual exposure to DBPs. Energy expenditure during swimming, atopy, and CC16 genotype (rs3741240) were also determined.Median serum CC16 levels increased from 6.01 to 6.21 microg/L (average increase, 3.3%; paired Wilcoxon test p = 0.03), regardless of atopic status and CC16 genotype. This increase was explained both by energy expenditure and different markers of DBP exposure in multivariate models. FeNO was unchanged overall but tended to decrease among atopics. We found no significant changes in lung function, SP-D, 8-isoprostane, eight cytokines, or VEGF.We detected a slight increase in serum CC16, a marker of lung epithelium permeability, in healthy adults after they swam in an indoor chlorinated pool. Exercise and DBP exposure explained this association, without involving inflammatory mechanisms. Further research is needed to confirm the results, establish the clinical relevance of short-term serum CC16 changes, and evaluate the long-term health impacts.
Granulomatous prostatitis. A mimic of carcinoma of the prostate
Authors: P. P. Kelalis
Journal: JAMA (1965)

In 70 cases of granulomatous prostatitis 54 (77%) mimicked carcinoma clinically. Granulomatous prostatitis is a distinct clinical and pathological entity, apparently a reaction to extravasated prostatic secretions into the surrounding tissues secondary to obstruction and infection within the prostate. In about 80% of the patients, there was a triad of (1) high fever followed by (2) symptoms of nonspecific prostatitis and (3) suggestion of a malignant prostate on rectal palpation. These features should suggest a presumptive diagnosis of granulomatous prostatitis, although histological confirmation is desirable. The disease occurs at a slightly earlier age than prostatic carcinoma. Empirical nonsurgical treatment will suffice in most cases if sufficient time is allowed for the inflammatory reaction to resolve. This seldom requires more than three months.
Clinical Crossroads: An 88-Year-Old Woman Facing the End of Life-Reply
Authors: Joanne Lynn
Journal: JAMA (1997)

In Reply.  —An ordinary dying person, an elderly woman with end-stage heart failure, cannot count on good care in our patchwork system. Our needs when dying of chronic disease in old age are mismatched with a service system bent on rescue. Each of these letters advocates the service approach of the author(s). Most likely, however, reform will require learning new arrangements that make good care routine. We need a few years of vigorous innovation and research, aiming to learn how to regularly ensure worthy living in that last phase of life. Otherwise, our inefficient and often ineffective system will soon be overwhelmed by the large number of baby boomers facing the end of life together. Dr Solomon may be correct that managed care offers opportunities for improvement, although the evidence to date is disheartening. The adjusted rate of mortality in Medicare managed care is only 63% of expected, 1 whereas the Veterans
Assurance Office Fees
Authors: W. C. Ford
Journal: BMJ (1843)

71of opium, yet " he was decidedly of opinion that the child's death was caused by opium."Dr. Babington also thought the remedy, not the disease, produced death.He tells us the heart disease arose from "a difficulty of propelling blood," but does not say how he knows that the enlargement of the heart was not congenital.It should not become fashionable to punish one mani upoIi the speculative opinions and theories of other men.We suppose tliat, generally speaking, when there are doubts, the accused party will have the benefit of them; but, as far as I am able to judge from experience, this verdict was given against the party accused, under false im- pressions, not upon facts.Anid if the judgment of the medical men of England were takeni by vote, whe- ther the evidence givell at that inquest or these remnarks and opinions are thc most reasonable, I should not fear the result.Remaining, Gentlemen,
Reduced lymphocyte stimulatory guanine nucleotide regulatory protein and beta-adrenergic receptors in congestive heart failure and reversal with angiotensin converting enzyme inhibitor therapy.
Authors: E M Horn, S J Corwin, S F Steinberg, Y K Chow, G W Neuberg, P J Cannon, E R Powers, J P Bilezikian
Journal: Circulation (1988)

Adrenergic hyporesponsiveness in congestive heart failure has been understood previously in terms of a reduction in beta-adrenergic receptors. We have examined another hypothesis, one that states the stimulatory guanine nucleotide regulatory protein (Gs) that couples the beta-adrenergic receptor to adenylate cyclase activity is also decreased in congestive heart failure. In addition to the 40% decrease in lymphocyte beta-adrenergic receptors in patients in congestive heart failure (5.9 +/- 0.7 vs. 9.7 +/- 1.4 fmol/mg, p less than 0.05), we found an 80% decrease in levels of Gs compared with age- and sex-matched healthy control subjects (72.5 +/- 19 vs. 376 +/- 73 fmol/mg, p less than 0.05). Myocardial Gs levels correlated significantly with lymphocyte Gs levels. We also assessed the hypothesis that reductions in beta-adrenergic receptors and in Gs are reversible after successful therapy with angiotensin converting enzyme inhibitors. Treatment with either captopril or lisinopril was associated with clinical improvement, an increase in beta-adrenergic receptor density (from 5.5 +/- 0.7 to 8.7 +/- 1.5 fmol/mg), and a twofold increase in Gs levels (p less than 0.05). Thus, the data are compatible with Gs serving as an adaptable and reversible regulator of the adrenergic response in congestive heart failure. In view of the fact that Gs is a transducing element common to all hormones that stimulate cyclic adenosine 5'-monophosphate production, the observations could extend to other abnormal neurohumoral mechanisms in congestive heart failure.