tbuckley/cabot-search huggingface dataset:
Derivatives of Amsacrine: Determinants Required for High Activity Against Lewis Lung Carcinoma
Authors: B. C. Baguley, G. J. Finlay
Journal: JNCI Journal of the National Cancer Institute (1988)

Antitumor activity against the Lewis lung carcinoma in mice is reported for the series of 36 acridine-substituted derivatives of the antileukemia agent amsacrine. This series is the one from which the analogue N, 5-dimethyl-9-[(2-methoxysulfonylamino)phenylamino]-4-acridinecarboxamide (CI-921), presently in clinical trial, was chosen. The analogues also were tested in vitro by comparing growth inhibition data [IC50 values (concentration required to reduce growth of cultured cells to 50% of that of untreated cultures)], using L1210 murine leukemia cells and HCT-8 human colon carcinoma cells. Determined IC50 values were highly dependent on the culture medium used, and it was found that the presence of ascorbate in the medium had a major effect on the stability of compounds to oxidation. A survey of 115 analogues of amsacrine indicates that a low ratio of IC50 values (HCT-8/L1210) is necessary but not sufficient for good antitumor activity against the solid tumor. DNA binding constants did not in themselves predict activity, although they were related to dose potency. Other factors, such as drug lipophilicity, acridine base strength, and drug solubility, also are involved, probably in providing effective drug distribution. It is concluded that in vitro assay data provide information useful for drug design but that other factors also are important for in vivo activity. [J Natl Cancer Inst 1988;80:195–199]
Margin, Ischemia, and Complications (MIC) Score in Partial Nephrectomy: A New System for Evaluating Achievement of Optimal Outcomes in Nephron-sparing Surgery
Authors: Nicolòmaria Buffi, Giuliana Lista, Alessandro Larcher, Giovanni Lughezzani, Vincenzo Ficarra, Andrea Cestari, Massimo Lazzeri, Giorgio Guazzoni
Journal: European Urology (2012)
Large conserved domains of low DNA methylation maintained by Dnmt3a
Authors: Mira Jeong, Deqiang Sun, Min Luo, Yun Huang, Grant A Challen, Benjamin Rodriguez, Xiaotian Zhang, Lukas Chavez, Hui Wang, Rebecca Hannah, Sang-Bae Kim, Liubin Yang, Myunggon Ko, Rui Chen, Berthold Göttgens, Ju-Seog Lee, Preethi Gunaratne, Lucy A Godley, Gretchen J Darlington, Anjana Rao, Wei Li, Margaret A Goodell
Journal: Nature Genetics (2013)
Distribution and kinetics of PBB residues in cattle.
Authors: G F Fries, G S Marrow, R M Cook
Journal: Environmental Health Perspectives (1978)

Cows fed a constant amount of polybrominated biphenyl (PBB) reached a steady-state concentration in milk fat within 30 days. This concentration was approximately four times the concentration in the total diet. When feeding of PBB was stopped, the concentration in milk was adequately described as a sum of two first-order elimination rates. Biological half-life in environmentally contaminated cows, studied for 6 months about a year after contamination, was 60 days. The stage of lactation affected the rate of elimination, and in some concentrations increased shortly after calving. Residues were distributed in body tissues proportionally to concentration of fat in the tissues. Liver and brain were exceptions. Concentration in liver fat was generally higher than other tissues and possibly related to the treatment of some cows with phenobarbital. Residues in brain fat were significantly lower than all other tissues. The ratio of the concentrations in milk fat to concentration of residues in the blood of calves and fat of fetal tissues to the concentration in the corresponding tissue in the dams was 0.36:1. It was estimated that people consuming milk from the highly contaminated Michigan cows could have received PBB doses as great as 10 g from this source alone.
Impulse oscillometry in comparison to spirometry in pregnant asthmatic females
Authors: K. Bidad, H. Heidarnazhad, A. Kazemnejad, Z. Pourpak
Journal: European Respiratory Journal (2008)

They are frequently multiple and bilateral, and present at a mean age of 50.7 yrs [7].The most common histological subtypes are hybrid oncocytic (50%) and chromophobe (34%) renal cell carcinoma, while clear cell, oncocytoma and papillary renal cell cancer are less frequently found [7].Radiographic screening is recommended, with a typical strategy involving abdominal computed tomography and/or renal ultrasound at the time of diagnosis, followed by interval screening every 3-5 yrs [8].Parenchyma-sparing surgery is recommended given the risk of development of further tumours [7].In line with these recommendations, all participants in the study by FRO ¨HLICH et al.[1] were screened for kidney manifestations by abdominal ultrasound and none were identified.The importance of recognising the possibility of a diagnosis of Birt-Hogg-Dube ´syndrome in patients with familial recurrent pneumothorax, with or without characteristic skin findings, lies in undertaking surveillance for renal tumours, a potentially lethal feature of this syndrome.
Not reading and signing letters you have dictated is dangerous
Authors: S. Shere
Journal: BMJ (2001)

EDITOR—For some time I have been unhappy at the number of letters that I receive unsigned, usually from fellow consultants but more recently also from general practitioners. After the warm best wishes at the end of the letter they usually state “Dictated but sent unsigned to avoid delay”; as we both know, this is almost always totally untrue.

I know many consultants who virtually never sign their letters and, worryingly, never read them after dictating them. To add insult to injury, I …
Basal Expression of Bone Morphogenetic Protein Receptor Is Reduced in Mild Asthma
Authors: Harsha H. Kariyawasam, Georgina Xanthou, Julia Barkans, Maxine Aizen, A. Barry Kay, Douglas S. Robinson
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

Despite increasing recognition of bone morphogenetic protein (BMP) signaling in tissue remodeling, the expression pattern of ligands and signaling pathways remain undefined in the asthmatic airway.To determine expression of BMP ligands (BMP-2, BMP-4, and BMP-7) and type I and type II receptors (ALK-2, ALK-3, ALK-6, and BMPRII) as well as evidence for activation of BMP signaling via detection of phosphorylated Smad1/5 (pSmad1/5) expression in asthmatic airways at baseline (compared with nonasthmatic controls), and after allergen challenge.Bronchial biopsies were obtained from 6 nonasthmatic control volunteers, and 15 atopic patients with asthma (median age, 25 yr; median FEV(1)% predicted, 97%) at baseline, then at 24 hours and 7 days after allergen challenge. Expression of BMP ligands, receptors, and signaling was analyzed using immunohistochemistry.BMP ligand expression did not differ between asthmatic and control airways at baseline. Compared with the normal airway, there was significant down-regulation of ALK-2 (P = 0.001), ALK-6 (P = 0.0009), and BMPRII (P = 0.009) expression in asthma. Allergen challenge was associated with marked and sustained up-regulation of BMP-7 in airway epithelium (P = 0.017) and infiltrating inflammatory cells (P = 0.071) (predominantly in eosinophils, but also CD4(+) T cells, mast cells, and macrophages). Up-regulation of pSmad1/5 expression (P = 0.031), ALK-2 (P = 0.002), and ALK-6 (P < 0.001) was observed indicating active signaling.BMP receptor expression is down-regulated in the asthmatic airway, which may impede repair responses. Allergen provocation increases expression of the regulatory ligand BMP-7, activates BMP signaling, and increases receptor expression, all of which may contribute to repair and control of inflammation.
Tolerance to Chemotherapy After Prior Irradiation for Hodgkin's Disease
Authors: Robert E. Curran, Ralph E. Johnson
Journal: Annals of Internal Medicine (1970)

Although intensive radiotherapy is generally well tolerated by patients with Hodgkin's disease, such treatment significantly reduces the bone marrow reserve. The hematologic tolerance to chemotherapy was evaluated in patients who had received prior irradiation. The important factors in determining the postirradiation tolerance to chemotherapy were extent of bone marrow irradiated and the time interval from completion of radiotherapy to onset of chemotherapy. Inability to deliver adequate chemotherapy after extensive radiotherapy was associated with both failure to achieve drug-induced remissions and limited survival times. This experience serves to emphasize the necessity for a rigorous diagnostic evaluation for each patient before institution of radical radiotherapy. Failure to carefully investigate the extent of disease, especially with respect to extranodal involvement, can only result in a radiation-induced reduction of bone marrow reserve which may prevent the subsequent administration of effective (though palliative) chemotherapy.
Endothelial Cilia Are Essential for Developmental Vascular Integrity in Zebrafish
Authors: Sowjanya Kallakuri, Jianxin A. Yu, Jade Li, Yuanyuan Li, Brant M. Weinstein, Stefania Nicoli, Zhaoxia Sun
Journal: Journal of the American Society of Nephrology (2014)

The cilium is a signaling platform of the vertebrate cell. It has a critical role in polycystic kidney disease and nephronophthisis. Cilia have been detected on endothelial cells, but the function of these organelles in the vasculature remains incompletely defined. In this study, using genetic and chemical genetic tools in the model organism zebrafish, we reveal an essential role of cilia in developmental vascular integrity. Embryos expressing mutant intraflagellar transport genes, which are essential and specific for cilia biogenesis, displayed increased risk of developmental intracranial hemorrhage, whereas the morphology of the vasculature remained normal. Moreover, cilia were present on endothelial cells in the developing zebrafish vasculature. We further show that the involvement of cilia in vascular integrity is endothelial autonomous, because endothelial-specific re-expression of intraflagellar transport genes in respective mutants rescued the intracranial hemorrhage phenotype. Finally, whereas inhibition of Hedgehog signaling increased the risk of intracranial hemorrhage in ciliary mutants, activation of the pathway rescued this phenotype. In contrast, embryos expressing an inactivating mutation in pkd2, one of two autosomal dominant cystic kidney disease genes, did not show increased risk of developmental intracranial hemorrhage. These results suggest that Hedgehog signaling is a major mechanism for this novel role of endothelial cilia in establishing vascular integrity.
CONSEQUENCES AND TREATMENT FROM A SURGICAL POINT OF VIEW
Authors: W. A. Lane
Journal: BMJ (1913)

MEDICAL JOURNAJ D.As the stomach is the place where the food first rests and remains longest, it possesses the most efficacious antitoxic properties.The healthy stomach is sterile, and all food during its stay within its cavity is sterilized as a result of peptic digestion, and this is carried oult in the
Will adopting the Canadian criteria improve diagnosis of CFS?
Authors: P. D. White, A. Miller, E. Crawley
Journal: BMJ (2011)

This study examined the ionic mechanism of ibutilide, a class III antiarrhythmic in clinical use, on freshly isolated human atrial cells. Cells had resting potentials of −71.4 ± 2.4 mV, action potentials with overshoot of 36.8 ± 1.8 mV, duration of 265 ± 89 msec at 90% repolarization and slow repolarization (<i>n</i> = 16). Ibutilide, at 10<sup>−</sup><sup>7</sup> M, markedly increased action potential duration. Four types of outward currents were detected: I<sub>to</sub>, I<sub>so</sub>, a delayed rectifier and I<sub>K1</sub>. Ibutilide had no inhibitory effect on these outward currents at 10<sup>−</sup><sup>7</sup> M (<i>n</i> = 28). In K<sup>+</sup>-free solutions and −40 mV holding potential, mean peak inward current at 20 mV was −1478 ± 103 pA (<i>n</i> = 12). Ibutilide increased this current to −2347 ± 75 pA at 10<sup>−</sup><sup>7</sup> M, with half maximal effect (<i>K</i><sub>d</sub>) of 0.1 to 0.9 nM between −10 and +40 mV (<i>n</i> = 21). At similar concentrations, the drug increased APD, with<i>K</i><sub><i>d</i></sub> of 0.7 and 0.23 nM at 70 and 90% repolarization, respectively (<i>n</i> = 8). Ibutilide shifted the mid-point of the steady-state inactivation curve from −21 to −12.2 mV (<i>n</i> = 6), and reduced current decline during repetitive depolarization (<i>n</i> = 5). The drug induced inward current was carried by Na<sup>+</sup><sub>o</sub> through a nifedipine inhibited inward channel because Na<sup>+</sup><sub>o</sub> removal eliminated the effect, and nifedipine abolished the inward current and the drug induced APD prolongation. We propose that a Na<sup>+</sup> current through the L-type Ca<sup>++</sup> channel mediates ibutilide’s potent clinical class III antiarrhythmic action.
Consumer Group Asks FDA to Warn Patients About Hypertension Combination Therapy
Authors: Mike Mitka
Journal: JAMA (2012)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Trends in Incident Hemodialysis Access and Mortality
Authors: Mahmoud B. Malas, Joseph K. Canner, Caitlin W. Hicks, Isibor J. Arhuidese, Devin S. Zarkowsky, Umair Qazi, Eric B. Schneider, James H. Black, Dorry L. Segev, Julie A. Freischlag
Journal: JAMA Surgery (2015)

Based on evidence of survival benefit when initiating hemodialysis (HD) via arteriovenous fistula (AVF) or arteriovenous graft (AVG) vs hemodialysis catheter (HC), the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative published practice guidelines in 1997 recommending 50% or greater AVF rates in incident HD patients. A decade after, lapses exist and the impact on HD outcomes is uncertain.To assess the achievement of the practice goals for incident vascular access and the effects on HD outcomes.This retrospective cohort study was conducted using the US Renal Data System. All patients with end-stage renal disease in the United States without prior renal replacement therapy who had incident vascular access for HD created between January 1, 2006, and December 31, 2010 (N = 510 000) were included.Incident vascular access use rates and mortality. Relative mortality was quantified using multivariable Cox proportional hazard models. Coarsened exact matching and propensity score-matching techniques were used to better account for confounding by indication.Of 510 000 patients included in this study, 82.6% initiated HD via HC, 14.0% via AVF, and 3.4% via AVG. Arteriovenous fistula use increased only minimally, from 12.2% in 2006 to 15.0% in 2010. Patients initiating HD with AVF had 35% lower mortality than those with HC (adjusted hazard ratio, 0.65; 95% CI, 0.64-0.66; P < .001). Those initiating HD with AVF had 23% lower mortality than those initiating with an HC while awaiting maturation of an AVF (adjusted hazard ratio, 0.77; 95% CI, 0.76-0.79; P < .001).Current incident AVF practice falls exceedingly short years after recommendations were made in 1997. The impact of this shortcoming on mortality for patients with end-stage renal disease is enormous. Functioning permanent access at initiation of HD confers lower mortality even compared with patients temporized with an HC while awaiting maturation of permanent access. A change of current policies and structured multidisciplinary efforts are required to establish matured fistulae prior to HD to ameliorate this deficit in delivering care.
Liver plasma membrane: The source of high molecular weight alkaline phosphatase in human serum
Authors: Marc E. De Broe, Frank Roels, Etienne J. Nouwen, Lutgarde Claeys, Roger J. Wieme
Journal: Hepatology (1985)

This study presents biochemical, histochemical, morphological and immunological evidence that part of the high molecular weight alkaline phosphatase observed in the serum of patients with liver disease and particularly in cases of intrahepatic cholestasis or focal–, extrahepatic obstruction originates from the liver plasma membrane. The high molecular weight protein alkaline phosphatase complex contains several plasma membrane enzymes and behaves like a plasma membrane fragment after isopycnic density gradient ultracentrifugation in sucrose, cesium chloride and metrizamide. Electron microscopic examination revealed a triple–layered vesicle which retained alkaline phosphatase activity. Incubation of human liver cells with anti–serum against purified high molecular weight multienzyme complex resulted in fixation of antibodies on the plasma membrane as shown by positive plasma membrane fluorescence. These plasma membrane fragments in the serum are not of biliary origin.
Evaluation of the Ephedrine Test
Authors: Peter P. Bosomworth
Journal: JAMA (1963)

<h3>To the Editor:</h3> —At the AMA meeting in June, 1961, Dr. Crandell mentioned the "ephedrine response test" as a method of screening for surgery patients who had been receiving reserpine. He did not present confirming clinical data, nor has he done so subsequently to the best of our knowledge. Such a test, if indeed it were accurate in predicting hypotension in reserpinized patients, would appear to be a useful clinical tool. We were interested in investigating the proposed test. We tried to utilize the test under clinical circumstances for patients receiving reserpine and also other compounds known to produce a hypotensive effect in the anesthetized patient. While the size of the series does not permit statistically valid conclusions that the test is useful, it did indicate that it was not reliable in predicting hypotension in the anesthetized patients previously treated with reserpine. Any additional data collected to test Dr. Crandell's
From Outcomes Research to Disease Management: A Guide for the Perplexed
Authors: Robert S. Epstein
Journal: Annals of Internal Medicine (1996)

Outcomes research is a rapidly evolving field that incorporates epidemiology, health services research, health economics, and psychometrics.Measurement of clinical and other outcomes has become increasingly important to the stakeholders in a rapidly changing health care environment. The desire to improve outcomes and control costs has stimulated greater interest in cost-effectiveness studies, which determine how well effective therapies work in the usual practice setting and how much they cost. The application of outcomes principles to the practices of health care providers has resulted in efforts to implement disease management programs. Unlike traditional programs carried out by physicians, these new efforts are based on systematic population-based approaches to identifying persons at risk, intervening with specific programs of care, and measuring clinical and other outcomes. The new efforts depend heavily on modern information systems.
Natural Course of Moderate Cardiac Allograft Rejection (International Society for Heart Transplantation Grade 2) Early and Late After Transplantation
Authors: Hans P. Brunner-La Rocca, Gabor Su¨tsch, Jakob Schneider, Ferenc Follath, Wolfgang Kiowski
Journal: Circulation (1996)

Background The significance of International Society for Heart Transplantation (ISHT) grade 2 cardiac allograft rejection has been questioned, and the medical community is not in complete agreement as to its clinical management. We therefore retrospectively analyzed the follow-up of all available endomyocardial biopsy samples obtained from 161 transplant patients since introduction of the ISHT nomenclature at our institution. Methods and Results Of 2868 biopsies performed 3 days to 8.9 years after transplantation, 420 biopsies had no follow-up or were preceded by intensified immunosuppression and were excluded from analysis. Of the remaining 2448 biopsies, 374 (15.3%) were repeat biopsies performed 7 to 10 days after prior ISHT 2 rejection without change of treatment. Of these, 70 (18.7%) had progressed to ≥ISHT 3A, whereas 82 (21.9%) remained unchanged and 222 (59.4%) resolved. In contrast, follow-up of 2074 biopsies with lower-grade rejection showed graft rejection classified as ≥ISHT 3A in 153 (7.4%), ISHT 2 in 240 (11.6%), and ≤ISHT 1B in 1681 (81.1%) biopsy samples ( P &lt;.0001). In univariate analysis, the odds ratio (OR) of graft rejection ≥ISHT 3A after ISHT 2 rejection was 2.89. Other univariate predictors of rejection ≥ISHT 3A were time after transplantation (OR=0.96 per month, P &lt;.0001), blood group type B (OR=1.62, P &lt;.005), “Quilty” lesion on previous biopsy (OR=1.70, P &lt;.005), number of HLA mismatches (OR=1.27 per mismatch, P &lt;.005), female sex (OR=1.55, P &lt;.05), and serum creatinine level (OR=0.93 per 10 μmol/L, P &lt;.005). Young age of recipients was a risk factor during long-term (≥2 years) follow-up ( P &lt;.002), and lower cyclosporine level was a risk factor during the first month after transplantation ( P &lt;.01). In multivariate logistic regression analysis, ISHT 2 rejection on previous biopsy remained the strongest predictor of rejection ≥ISHT 3A (OR=2.40, P &lt;.0001). Conclusions Several factors independently increase the risk of rejection classified as ≥ISHT 3A. The strongest predictor of a grade of ≥ISHT 3A was ISHT 2 rejection on the previous biopsy obtained 7 to 10 days earlier. Therefore, ISHT 2 graft rejection is of clinical significance, and short-term follow-up appears to be warranted even late after transplantation.
Unilateral Edema and Jaundice After Portacaval Anastomosis
Authors: HAROLD O. CONN
Journal: Annals of Internal Medicine (1972)

Unilateral edema may occur after portacaval anastomosis or other right-sided laparotomies in cirrhotic patients with ascites. This unusual pattern of fluid retention apparently develops as a consequence of operative communications between the peritoneal cavity and the subcutaneous tissue, especially with disruption of deeper layers of the wound. Ascitic fluid passes through these fistulas into the subcutaneous tissue and dissects to dependent portions of the body, including the scrotum and sometimes the ipsilateral lower extremity. Unilateral jaundice may develop as part of this phenomenon because of the presence of a relatively large amount of bilirubin bound to the albumin of the ascitic fluid, which had dissected subcutaneously. The edema distribution may be bilateral when incisions cross the midline and presumably may be left-sided after left-sided surgery. These phenomena may occur in noncirrhotic patients with postoperative ascites.