tbuckley/cabot-search huggingface dataset:
Was the Atrial Septal Defect Closed?
Authors: Alan L. Saroff
Journal: JAMA (1988)

<h3>To the Editor.</h3> —The Sept 18 issue of<i>JAMA</i>carried a letter entitled "Persistence of Enlarged Pulmonary Arteries—22 Years After Atrial Septal Defect Closure."<sup>1</sup>The letter describes markedly dilated pulmonary vessels in a patient who presumably had his atrial septal defect successfully closed 22 years prior to the observation. Unfortunately, Gould and associates do not conclusively demonstrate that the atrial septal defect was adequately closed. There was no mention of any attempt to demonstrate a step-up in oxygen saturation at the right atrial level and no hydrogen arrival time procedure was carried out. No mention is made of the second heart sound. This should show fixed splitting if the atrial septal defect were still present, but should be normally split (moving with respiration) if the defect had been successfully closed.
Benzoic acid metabolism reflects hepatic mitochondrial function in rats with long-term extrahepatic cholestasis
Authors: L Krähenbühl, J Reichen, C Talos, S Krähenbühl
Journal: Hepatology (1997)

Benzoic acid metabolism, which is primarily a function of liver mitochondria, depending on the concentration of adenosine triphosphate (ATP), coenzyme A (CoA), and glycine in the mitochondrial matrix, was investigated in both rats with long-term cholestasis caused by bile duct ligation (BDL) and sham-operated control rats. In isolated liver mitochondria, hippurate production from benzoate in the presence of saturating glycine concentrations was reduced in BDL rats by 36% with L-glutamate as a source for ATP, by 21% in the presence of succinate, and by 31% in the presence of ATP plus oligomycine. This reduction in benzoate metabolism is in the same range as the previously observed reduction in the activity of the electron transport chain in liver mitochondria from BDL rats. The mitochondrial CoA pool, which can be rate-limiting for benzoic acid metabolism, was not different between BDL and control rats. The activity of benzoyl-CoA synthase, the enzyme catalyzing the rate-limiting step in benzoate metabolism, was reduced by 25%, and the activity of benzoyl-CoA:glycine N-transferase was reduced by 66% in BDL rats. The activity of benzoyl-CoA synthase was significantly inhibited by lithocholate, suggesting that hepatic accumulation of hydrophobic bile acids could contribute to the observed reduction of benzoate metabolism in BDL rats. Benzoate metabolism was also studied in vivo by monitoring the urinary hippurate excretion after intraperitoneal administration of benzoate (100 micromol/100 g of body weight). The time course of hippurate excretion was not different between BDL and control rats. Hippurate excretion over 24 hours after benzoate administration averaged 89.7 +/- 4.0% of the administered dose in BDL and 74.4 +/- 6.9% (mean +/- SEM, difference not significant) in control rats. This finding could be explained by an increase in mitochondrial protein in BDL rats, averaging 2.34 +/- 0.29 g per liver in BDL and 1.35 +/- 0.07 g per liver in control rats (mean +/- SEM, p < .05). Thus, the studies show that benzoate metabolism reflects mitochondrial function in BDL rats both in vivo and in vitro, and that mitochondrial proliferation compensates for the observed decrease in benzoic acid metabolism in isolated mitochondria in vitro.
German doctors criticise proposals for new law on assisted suicide
Authors: A. Tuffs
Journal: BMJ (2012)

German doctors, hospice organisations, and church representatives have criticised a draft law on helping terminally ill people to end their lives for its lack of clarity over who would be prosecuted.

The proposals, released by the Ministry of Justice in July, are the first attempt to establish a legal framework in Germany under which relatives or friends can help someone who is terminally ill to die. The draft bill says that doctors and nurses who have a personal relationship with the patient will also be able to help them die without legal recriminations.

The new law aims to stop organisations such as Dignitas Deutschland and Sterbehilfe (Euthanasia) Deutschland from operating …
452. Bone Marrow Stem Cells Are Potent Targets for Gene Therapy of Epidermolysis Bullosa, a Genetic Blistering Skin Disease
Authors: Katsuto Tamai, TaKehiko Yamazaki, Otsuru Satoru, Takenao Chino, Yasushi Kikuchi, Yasufumi Kaneda
Journal: Molecular Therapy (2006)

Pluripotency of bone marrow stem cell (BMSC) has been intensively investigated, and promoted new concept, i.e. BMSC-gene therapy, for various genetic diseases to regenerate gene-corrected tissues derived from BMSCs. Despite these intensive studies, the plasticity of BMSCs to the epidermal keratinocytes is still under controversial arguments. The rarity of the BMSCs-derived keratinocytes in vivo has led pessimistic view on the roles of BMSCs for maintenance of the epidermal structures. Here, we investigated our hypothesis that follicular and interfollicular epidermal stem/ progenitor cells may migrate, at least in part, from bone marrow to the engrafted new born mouse skin, which will newly develop abundant follicles and epidermal appendages as well as squamous epithelia under regional severe hypoxic condition. Concretely, the skin sheets of newborn and adult mice were surgically engrafted onto the back of 8 week-old mice with prior transplantation of GFP-transgenic bone marrow cells after lethal dose X-ray irradiation, and examined appearance of GFP-positive epidermal cells in the grafts in various time points. In a week after the skin grafting, dense migration of GFP+ mesenchymal cells appeared in the upper dermis of the newborn skin graft, whereas only sparse GFP+ cells in the adult skin graft were detected. In 2 to 4 weeks after engraftment, various regions of newly generated follicular and interfollicular epidermis were significantly composed of GFP+ keratinocytes, and some regions exhibited full thickness of GFP+ epidermis, suggesting existence of BMSCs-derived epidermal stem cells. Recruitment of the GFP-transgenic BMSCs to the skin graft was further enhanced by transplantation of the type VII collagen gene (COL7A1) null newborn mouse skin, which required rapid proliferation of the epidermal keratinocytes due to frequent detachment of the epidermis from the underlying dermis. The COL7A1 null skin graft exhibited more than 50% occupancy of the follicular and interfollicular epidermis with GFP+ keratinocytes at 4 weeks after engraftment. These data suggest that BMSCs may provide epidermal stem cells in the newborn skin, especially of severe epidermolysis bullosa patients. COL7A1 Gene-collected bone marrow cell transplantation in the blisters of dystrophic epidermolysis bullosa patients, who are suffering from defect of type VII collagen at the cutaneous basement membrane zone, would be potential strategy for effective gene therapy of this intractable genetic blistering skin disease.
Penicillin G Therapy in Renal Failure
Authors: D. CRAIG BRATER
Journal: Annals of Internal Medicine (1975)

Comments and CorrectionsJune 1, 1975Penicillin G Therapy in Renal FailureD. CRAIG BRATER, M.D.D. CRAIG BRATER, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-82-6-850_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The article by Bryan and Stone (Ann Intern Med82:189-195, 1975) is a welcome example of attempts by clinicians to apply pharmacokinetic concepts to drug use during renal failure for enhancement of efficacy with reduction in toxicity. Earlier guidelines for the use of drugs in renal impairment, as in this paper, have tended to advocate the administration of conventional or moderately reduced doses of drugs at long intervals (1). Less attention has been paid to the effects of giving small doses of the drug at conventional intervals to maintain more constant serum levels of the drug.The...References1. BENNETTSINGERCOGGINS WIC: Guide to drug usage in adult patients with impaired renal function. A supplement. JAMA 223:991-997, 1973 CrossrefMedlineGoogle Scholar2. O'GRADY F: Antibiotics in renal failure. Br Med Bull 27:142-147, 1971 CrossrefMedlineGoogle Scholar3. VAN GEMERTDUYFF AJ: Optimal dosage of drugs. Acta Physiol Pharmacol Neerl 1:256-278, 1950 MedlineGoogle Scholar4. CHANBENNERHOEPRICH REP: Gentamicin therapy in renal failure: a nomogram for dosage. Ann Intern Med 76:773-778, 1972 LinkGoogle Scholar5. EAGLEFLEISCHMANLEVY HRM: "Continuous" vs. "discontinuous" therapy with penicillin. The effect of the interval between injections on therapeutic efficacy. N Engl J Med 248:481-488, 1953 CrossrefMedlineGoogle Scholar1. SMITHLERNERWEINSTEIN HPL: Neurotoxicity and "massive" intravenous therapy with penicillin: a study of possible predisposing factors. Arch Intern Med 120:47-53, 1967 CrossrefMedlineGoogle Scholar2. MAWERAHMADDOBBS GRS: Prescribing aids for gentamicin. Br J Clin Pharmacol 1:45-50, 1974 CrossrefMedlineGoogle Scholar3. VAN SAANEN P: Kinetic studies and their value for a better dosage schedule of antibiotics. I. The penicillins. Rev Roum Med Intern 10:149-157, 1973 MedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics June 1, 1975Volume 82, Issue 6Page: 850-851KeywordsAntibioticsPenicillin Issue Published: June 1, 1975 PDF DownloadLoading ...
Protease-Activated Receptor 1 Mediates Thrombin-Dependent, Cell-Mediated Renal Inflammation in Crescentic Glomerulonephritis
Authors: Malcolm A. Cunningham, Eric Rondeau, Xin Chen, Shaun R. Coughlin, Stephen R. Holdsworth, Peter G. Tipping
Journal: The Journal of Experimental Medicine (2000)

Protease-activated receptor (PAR)-1 is a cellular receptor for thrombin that is activated after proteolytic cleavage. The contribution of PAR-1 to inflammatory cell–mediated renal injury was assessed in murine crescentic glomerulonephritis (GN). A pivotal role for thrombin in this model was demonstrated by the capacity of hirudin, a selective thrombin antagonist, to attenuate renal injury. Compared with control treatment, hirudin significantly reduced glomerular crescent formation, T cell and macrophage infiltration, fibrin deposition, and elevated serum creatinine, which are prominent features of GN. PAR-1–deficient (PAR-1−/−) mice, which have normal coagulation, also showed significant protection from crescentic GN compared with wild-type mice. The reductions in crescent formation, inflammatory cell infiltration, and serum creatinine were similar in PAR-1−/− and hirudin-treated mice, but hirudin afforded significantly greater protection from fibrin deposition. Treatment of wild-type mice with a selective PAR-1–activating peptide (TRAP) augmented histological and functional indices of GN, but TRAP treatment did not alter the severity of GN in PAR−/− mice. These results indicate that activation of PAR-1 by thrombin or TRAP amplifies crescentic GN. Thus, in addition to its procoagulant role, thrombin has proinflammatory, PAR-1–dependent effects that augment inflammatory renal injury.
Vitamins C and B12
Authors: Mehr Afroz
Journal: JAMA (1975)

<h3>To the Editor.—</h3> The spinal cord injury service at our hospital brings us in contact with a large number of patients at high risk for urinary tract infections. Thus, we read with great interest the recent article by Herbert and Jacob (230:241, 1974) regarding the in vitro destruction of vitamin B<sub>12</sub>by ascorbic acid. As a routine procedure, all of the spinal cord injury patients on our service receive doses of ascorbic acid of or more than 4 gm/day to enhance urinary acidity. We measured serum vitamin B<sub>12</sub>levels by the technique of radioisotope displacement in ten male patients, aged 17 to 69 years. Each of these patients had received ascorbic acid in this dose for more than 11 months. All had been on unrestricted diets and all took their medication in four divided doses each day. The vitamin B<sub>12</sub>levels were all well above the low
Risk Factors for Ectopic Pregnancy-Reply
Authors: Robert N. Taylor
Journal: JAMA (1988)

<h3>In Reply.—</h3> I am pleased to respond to the comments by Dr Jones on my article inTHE JOURNAL. It is important to emphasize that the presence of pathogenic microorganisms in the endocervix does not prove that such microbes are causally associated with upper genital tract infections. The study to which I referred reported the prevalence of<i>Neisseria gonorrhoeae</i>recovered from the fallopian tubes and peritoneal cavities of women with acute salpingitis.<sup>1</sup>Although nearly 50% of these patients had endocervical cultures that were positive for<i>N gonorrhoeae</i>, this organism was isolated from the fallopian tubes in only 23% of cases. I concur fully with the opinion of Dr Jones that broad-spectrum antibiotic therapy, including agents effective against gonococci, chlamydiae, and anaerobes, should be instituted promptly when the clinical or laparoscopic diagnosis of salpingitis is made. Indeed, this is the recommendation of the Centers for Disease Control.<sup>2</sup>Practitioners should
Carriage of the PNPLA3 rs738409 C &gt;G polymorphism confers an increased risk of non-alcoholic fatty liver disease associated hepatocellular carcinoma
Authors: Y.-L. Liu, G.L. Patman, J.B.S. Leathart, A.-C. Piguet, A.D. Burt, J.-F. Dufour, C.P. Day, A.K. Daly, H.L. Reeves, Q.M. Anstee
Journal: Journal of Hepatology (2014)
EARLY AND LATE DISCONTINUATION OF ORAL ANTIPLATELET THERAPY AFTER DES IMPLANTATION: PREVALENCE, PREDICTORS, AND LONG-TERM PROGNOSIS
Authors: Roberta Rossini, Corrado Lettieri, Giuseppe Biondi Zoccai, Giuseppe Musumeci, Tamar Nijaradze, Michele Romano, Nicola Cicorella, Nikoloz Lortkipanidze, Antonio Izzo, Vasile Sirbu, Antonello Gavazzi, Dominick J. Angiolillo, Ospedali Riuniti di Bergamo
Journal: Journal of the American College of Cardiology (2010)
Abstract 3841: 3D spheroid culture model for studying cancer progression: fine tuning the extracellular environment.
Authors: Gabriel J. Benton, Irina Arnaoutova, Jay George
Journal: Cancer Research (2013)

Abstract There is a need for more comprehensive and physiologically predictive cancer progression models. Tumor cell aggregates or spheroids are more demonstrative of tumors in vivo as they display several physiological traits including comparable morphology, reduced proliferation rates, elevated cell survival, cell-cell bond formation, tumor dormancy, and a hypoxic core. Embedding these spheroids in a physiological hydrogel composed of basement membrane proteins provides networks on which cells can travel out of the spheroid, mimicking early events during metastasis. Recent studies implicate the tumor microenvironment as a key component of the cancer progression process, and changes in tissue rigidity and collagen I content have been associated with this pathological process. The purpose of this study is to model the effects of differing extracellular matrix composition on morphology and invasiveness in different metastatic cell types during early metastatic events. Here, human cell lines representing different cancer types were grown in spheroid culture and subjected to embedding in hydrogels of differing extracellular matrix protein composition. The cell panel includes MDA-MB-231 for breast cancer, PC-3 for prostate cancer, U-87 MG for glioblastoma and HT-1080 for fibrosarcoma. Spheroids were photographed every 24 hours, and photographs were subjected to image analysis. The composition of the extracellular matrix hydrogel had a significant effect on the morphology of the invading cells as well as the rate of invasion. Increasing the collagen I content to model a more fibrotic environment resulted in fewer but longer process formation, representing a more motile cancer model; however, collagen I, alone, was insufficient to support robust invasion. In conclusion, the 3D spheroid invasion model suggests that the composition of the extracellular matrix proteins is important for cancer cell behavior during metastasis. Citation Format: Gabriel J. Benton, Irina Arnaoutova, Jay George. 3D spheroid culture model for studying cancer progression: fine tuning the extracellular environment. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3841. doi:10.1158/1538-7445.AM2013-3841
A Study in Cot Death
Authors: R. T. Cooke, R. G. Welch
Journal: BMJ (1964)

<h3>Abstract</h3> The outbreak of COVID-19 has caused serious epidemic events in China and other countries. With the rapid spread of COVID-19, it is urgent to explore the pathogenesis of this novel coronavirus. However, the foundational research of COVID-19 is very weak. Although angiotensin converting enzyme 2 (ACE2) is the reported receptor of SARS-CoV-2, information about SARS-CoV-2 invading airway epithelial cells is very limited. Based on the analysis of the Human Protein Atlas database, we compared the virus-related receptors of epithelial-derived cells from different organs and found potential key molecules in the local microenvironment for SARS-CoV-2 entering airway epithelial cells. In addition, we found that these proteins were associated with virus reactive proteins in host airway epithelial cells, which may promote the activation of the immune system and the release of inflammatory factors. Our findings provide a new research direction for understanding the potential microenvironment required by SARS-CoV-2 infection in airway epithelial, which may assist in the discovery of potential drug targets against SARS-CoV-2 infection.
Alcohol and Drugs Are Women's Issues, vol 2: The Model Program Guide
Authors: Joyce H. Lowinson
Journal: JAMA (1992)

This book is the second volume of a set published by the Women's Action Alliance, which is a nonprofit organization focused on addressing critical substance abuse. The goal of the Alliance is to build networks among women's organizations with a view toward creating consciousness, educating, mobilizing, and empowering. The first volume of the series presented an introduction to the key issues related to the connections between alcohol and drug abuse and how those impact on women and their families in the critical aspects of their lives. This book, according to the editor, provides a step-by-step guide to replicating the innovative, award-winning model program developed by the Women's Alcohol and Drug Education Project of the Women's Action Alliance and tested by six diverse women's centers in different regions of the country. The model program and guide focus on alcohol, drugs, and related issues most relevant for Latina, African-American, and low-income white
Complications of heparin administration in normal individuals
Authors: Kenneth A. Schwartz, George Royer, Donald B. Kautman, John A. Penner
Journal: American Journal of Hematology (1985)

Abstract The incidence, severity, and pathogenic mechanism of heparin‐associated thrombocytopenia with both bovine and porcine heparin administration were studied in forty normal males randomized to one of four treatment groups: beef lung heparin #1, beef lung heparin #2, porcine gut heparin, and saline control. All of the subjects receiving heparin developed a reversible increase in serum transaminases (SGOT, SGPT). However, other measurements of liver function were normal. Thirty‐three percent of these heparinized normals had decreased platelet counts. The incidence of platelet count decrease was similar for both bovine and porcine heparins, but 4 of the 20 normals receiving bovine heparin had platelet counts less than 150,000/μl. Immune pathogenesis was investigated by analyzing plasma from the volunteers for both platelet antibody and immune complexes. None of the men had increased plateletassociated IgG. Among the ten subjects with decreased platelet counts, IgG immune complexes were detected in three and C 1q in seven. The heparin‐associated thrombo‐cytopenia appears not to be mediated by a platelet antibody. More probably it reflects a direct effect of the heparin on platelets.
THE DISEASED MIDDLE TURBINATE.
Authors: CHARLES H. BAKER
Journal: JAMA (1903)

The undue importance which has been given the lower turbinate bodies in the search for the etiology of nasal disorders has overshadowed all other parts of the nasal cavities and led to wrongfully crediting the lower turbinate with the more important instead of the less important rôle in the production of nasal disease. This was principally owing to their easy accessibility and also to the fact that in most nasal disorders these bodies were found swollen and occluding the respiratory passages whereby effect was mistaken for cause. A moment's reflection will convince one that an acute coryza manifests itself in the region above the lower turbinate first, with a feeling of dryness and pressure followed later by obstruction to respiration due to swelling of the lower turbinate. Very often a patient presents himself with a beginning coryza in which the only perceptible change of the mucous surface is a dryness
Current management of hypertension in general practice.
Authors: R F Heller, G Rose
Journal: BMJ (1977)

An examination of the notes of 697 patients in a random sample of seven general practices in one part of inner London showed that 164 (24%) of 669 had had a blood-pressure recording in a five-year period. Proportions varied between 4% and 36% in the different practices. The blood pressure was raised (systolic greater than or equal to 160 mm Hg or diastolic greater than or equal to 100 mm Hg or both) in 74 patients (45%) whose blood pressure had been recorded, and another recording had subsequently been made in 45 (61%) of these patients. Fifteen (21%) of those with hypertension had not had a blood-pressure recording during the five years before the study. Tranquillisers or sedatives were the commonest drugs used in the treatment of hypertension. As in a study of the management of hypertension in hospital, opportunities provided by visits to the general practitioner were not commonly used for blood-pressure screening, and the discovery of hypertension often did not lead to further action.