tbuckley/cabot-search huggingface dataset:
Oral Penicillin in Children
Authors: S. A. Doxiadis, J. L. Emery, S. M. Stewart
Journal: BMJ (1951)

INDIVIDUAL OBSERVATIONS cocarboxylase and riboflavin in the treatment of '4 ** 3 ¢/^:diabetic acidosis -.X in human patients = control patients; * * = cocarbi oxylase-treated patients.is, of course, more difficult, s i n c e comparisons are valid only when comparable cases are contrasted; this was more easily achieved with the rabbits than with the patients.Thus, while we have confirmed the evidence of defective pyruvic acid oxi- dation in diabetic acidosis, we found no evidence that this was due to a deficiency of cocarboxylase.Normal pyruvic acid metabolism requires not only cocarboxy- lase and other co-enzymes but also the integrity of the enzyme protein; it may be that in diabetic acidosis the protein component of the enzyme system is inhibited or partially inactivated as it is in sodium arsenite poison- ing (Peters, Sinclair, and Thompson, 1946).SummaryThe blood pyruvic acid level was found raised during diabetic acidosis in 12 alloxan-diabetic rabbits and 4 acidotic diabetic patients.Supplementing a standard treatment for diabetic acidosis by cocarboxylase (vitamin B, diphosphate) and riboflavin did not appear to accelerate further the recovery from diabetic acidosis, as measured by the rate of the fall of the raised blood pyruvic acid level, the' fall of the blood sugar, the rise of the alkali reserve, or the observed clinical improve- ment.We wish to express our thanks to Dr. Russell Fraser for his help and advice, to
Cardiovascular Risk Assessment of the Liver Transplant Candidate
Authors: Zankhana Raval, Matthew E. Harinstein, Anton I. Skaro, Ata Erdogan, Andre M. DeWolf, Sanjiv J. Shah, Oren K. Fix, Nina Kay, Michael I. Abecassis, Mihai Gheorghiade, James D. Flaherty
Journal: Journal of the American College of Cardiology (2011)
Chloroquine Therapy in Rheumatoid Arthritis
Authors: Norman O. Rothermich
Journal: JAMA (1966)

To the Editor:—  Some physicians might interpret your editorial remarks ( 195 :774, 1966) to suggest that  therapy is not necessarily hazardous. I'm sure you did not intend to give this impression where it relates to long-term therapy in rheumatoid arthritis. It was stated that chloroquine therapy will not usually lead to ocular damage—in patients on low dosage.  However, few rheumatologists would expect appreciable benefit from  therapy in rheumatoid arthritis at a daily dose of less than 200 mg. Yet in the article by Henkind et al ( Arch Ophth  71 : 157, 1964) reference is made to a group of patients on a daily dose of 200 mg or more and all showed a significant elevation of their retinal threshold after the cumulative dose exceeded 100 gm.  In many communications on the subject, the feeling is expressed that where the retinopathy is detectable there are already large stores of
Acyclovir in chronic hepatitis B virus infection
Authors: Geoffrey M. Dusheiko
Journal: Hepatology (1988)

In a previous study a partial inhibition of viral replication was observed in HBeAg-positive patients after acyclovir (ACV) treatment. To assess those results and to evaluate different treatment regimens, a randomized controlled trial with ACV given at 45 mg/kg/day by continuous infusion (in 5 patients) or by intermittent 8-hourly infusion (in 6 patients) for 28 days versus placebo has been performed in 20 patients affected by chronic hepatitis positive for both HBsAg and HBeAg for at least 6 months. Patients were stratified for sex, presence of cirrhosis and homosexual activity. Modest inhibition of serum DNA polymerase activity was observed after intermittent ACV treatment but not with the continuous infusion. After a 8-12 months follow-up, 2 of 10 of the ACV-treated patients and 3 of the controls had become HBe-Ag-negative, with 1 and 2 seroconversions to anti-HBe in the treated and placebo group respectively. No adverse effects were observed in ACV-treated patients after continuous infusion, but 2 of 6 patients who received intermittent therapy had to stop treatment, because of abdominal colics and elevation of the serum creatinine. Our data confirm that ACV partially inhibits viral replication in HBeAg-positive patients but without significantly affecting the rate of seroconversion to anti-HBe. Histological remission is recognized to follow loss of viral replication in chronic hepatitis B virus infection. The aim of antiviral therapies has been to accelerate seroconversion from HBeAg to anti-HBe, but so far none has been shown to be of significant advantage in adequate, controlled trials and toxicity has been common. A randomized controlled trial of acyclovir, 45 mg/kg/day by continuous intravenous infusion for 28 days versus no therapy has been completed in 30 patients positive for HBsAg and HBeAg for a minimum of 6 months. Patients were stratified for sex, histology and homosexual activity. Twenty-eight days therapy was associated with only a modest reduction in serum markers of viral replication. At 12-months DNAp was lost in 5/15 treated and 2/11 of the untreated group, while of the latter, 2 patients initially negative became positive. Seroconversion from HBeAg to anti-HBe had occurred in 4 of 15 treated and 1 of 15 untreated patients (95% confidence limits 12% and 51%) and was associated with histological improvement. Acyclovir had only a weak effect on viral replication and did not significantly accelerate the rate of seroconversion to anti-HBe.
PREGNANCY DIAGNOSIS STATION: REPORT OF FOURTH YEAR'S WORKING
Authors: B. P. Wiesner
Journal: BMJ (1933)

Previous reports' dealt with the cases diagnosed by the station up to the end of January, 1932.The presert report refers to the work carried out between the end of January, 1932, and January 31st, 1933.As previously, only cases submitted by practitioners, hospitals, or public health authorities are considered.There will be a separate report on the results of tests undertaken on selected samples in connexion with certain clinical studies.In all 2,368 cases have been dealt with in the period of the report; this figure does not include repeatL tests.The total number of cases diagnosed since 1929 thus exceeds 5,500.TECIINIQUEThe modifications of the original technique which were introduced previously (routine detoxication with sulpho-
Progressive peripheral arterial occlusive disease and other vascular events during nilotinib therapy in CML
Authors: Karl J. Aichberger, Susanne Herndlhofer, Gerit‐Holger Schernthaner, Martin Schillinger, Gerlinde Mitterbauer‐Hohendanner, Christian Sillaber, Peter Valent
Journal: American Journal of Hematology (2011)

The second generation BCR/ABL kinase inhibitor nilotinib is increasingly used for the treatment of imatinib-resistant chronic myeloid leukemia (CML). So far, nilotinib is considered a well-tolerated drug with little if any side effects, although an increase in the fasting glucose level has been reported. We examined a series of 24 consecutive CML patients treated with nilotinib in our center for the development of non-hematologic adverse events. Three of these 24 CML patients developed a rapidly progressive peripheral arterial occlusive disease (PAOD) during treatment with nilotinib. In all three cases, PAOD required repeated angioplasty and/or multiple surgeries within a few months. No PAOD was known before nilotinib-therapy in these patients, although all three had received imatinib. In two patients, pre-existing risk factors predisposing for PAOD were known, and one of them had developed diabetes mellitus during nilotinib. In the other 21 patients treated with nilotinib in our center, one less severe PAOD, one myocardial infarction, one spinal infarction, one subdural hematoma, and one sudden death of unknown etiology were recorded. In summary, treatment with nilotinib may be associated with an increased risk of vascular adverse events, including PAOD development. In a subgroup of patients, these events are severe or even life-threatening. Although the exact mechanisms remain unknown, we recommend screening for pre-existing PAOD and for vascular risk factors such as diabetes mellitus in all patients before starting nilotinib and in the follow up during nilotinib-therapy.
Serotonin regulates pancreatic beta cell mass during pregnancy
Authors: Hail Kim, Yukiko Toyofuku, Francis C Lynn, Eric Chak, Toyoyoshi Uchida, Hiroki Mizukami, Yoshio Fujitani, Ryuzo Kawamori, Takeshi Miyatsuka, Yasuhiro Kosaka, Katherine Yang, Gerard Honig, Marieke van der Hart, Nina Kishimoto, Juehu Wang, Soroku Yagihashi, Laurence H Tecott, Hirotaka Watada, Michael S German
Journal: Nature Medicine (2010)
Significance of Diastolic Dysfunction of the Heart
Authors: B H Lorell
Journal: Annual Review of Medicine (1991)

CD40 is a cell-surface member of the TNF (tumor necrosis factor) receptor superfamily. Upon activation, CD40 can license dendritic cells to promote antitumor T cell activation and re-educate macrophages to destroy tumor stroma. Numerous agonist CD40 ...Read More
Characterization of fecal microbial communities in patients with liver cirrhosis
Authors: Yanfei Chen, Fengling Yang, Haifeng Lu, Baohong Wang, Yunbo Chen, Dajiang Lei, Yuezhu Wang, Baoli Zhu, Lanjuan Li
Journal: Hepatology (2011)

Liver cirrhosis is the pathologic end stage of chronic liver disease. Increasing evidence suggests that gut flora is implicated in the pathogenesis of liver cirrhosis complications. The aim of this study was to characterize the fecal microbial community in patients with liver cirrhosis in comparison with healthy individuals. We recruited 36 patients with liver cirrhosis and 24 healthy controls. The fecal microbial communities was analyzed by way of 454 pyrosequencing of the 16S ribosomal RNA V3 region followed by real-time quantitative polymerase chain reaction. Community-wide changes of fecal microbiota in liver cirrhosis were observed compared with healthy controls. The proportion of phylum Bacteroidetes was significantly reduced ( P = 0.008), whereas Proteobacteria and Fusobacteria were highly enriched in the cirrhosis group ( P = 0.001 and 0.002, respectively). Enterobacteriaceae ( P = 0.001), Veillonellaceae ( P = 0.046), and Streptococcaceae ( P = 0.001) were prevalent in patients with cirrhosis at the family level. A positive correlation was observed between Child-Turcotte-Pugh (CTP) score and Streptococcaceae ( R = 0.386, P = 0.02). Lachnospiraceae decreased significantly in patients with cirrhosis ( P = 0.004) and correlated negatively with CTP score ( R = −0.49, P = 0.002). Using partial least square discriminate analysis, we identified 149 operational taxonomic units (OTUs) as key phylotypes that responded to cirrhosis, most of which were Lachnospiraceae (65 OTUs), Streptococcaceae (23 OTUs), and Veillonellaceae (21 OTUs). Conclusion: Fecal microbial communities are distinct in patients with cirrhosis compared with healthy individuals. The prevalence of potentially pathogenic bacteria, such as Enterobacteriaceae and Streptococcaceae , with the reduction of beneficial populations such as Lachnospiraceae in patients with cirrhosis may affect prognosis. (Hepatology 2011;)
Ventricular function. Is the total more than the sum of the parts?
Authors: D L Brutsaert, S U Sys
Journal: Circulation (1991)

For the life of the body is more than the sum of the properties of the cells of which it is composed.D'Arcy Wentworth Thompson (based on a statement by Goethe)l F undamental to evolution in biology has been the trend toward growing complexity, from the molecular to the cellular level, toward multicellularity, and finally the whole-organ level.At any level, biological systems are composed of inter- acting subsystems, which in turn are also systems, albeit on a smaller scale.Interaction between sub- systems may add entirely new properties to the composite system.In the cardiovascular system, con- sideration of the interaction between the left ventri- cle and arterial load and the efficiency of this inter- action is not new.2-4In the heart, already on smaller scales, several interaction processes seem to be in- corporated as we move up from a subcellular to the whole-organ level (Figure 1).From the subsequent discussion on ventricular function, it will follow that interaction processes constitute an essential and obligatory property of ventricular function, in which the mechanisms involved are still largely unknown.Therefore, one cannot easily extrapolate from mere subcellular or molecular events to whole-organ func- tion without considering these interaction processes at increasingly larger levels.Several interaction processes have been considered at different levels.We will focus on three of these: Upgrading of system performance through interaction of subsystems, uniformity of system performance through interaction of subsystems, and modulation of system performance through cell communication.Upgrading of System Performance Through Interaction of Subsystems The most generally accepted model of cardiac contraction at the molecular level is the cyclical attachment and detachment of the globular portion
Angiotensin II Induces DNA Damage in the Kidney
Authors: Ursula Schmid, Helga Stopper, Frank Schweda, Nina Queisser, Nicole Schupp
Journal: Cancer Research (2008)

Abstract Increased activity of the renin angiotensin system with enhanced levels of angiotensin II leads to oxidative stress with endothelial dysfunction, hypertension, and atherosclerosis. Epidemiologic studies revealed a higher cancer mortality and an increased kidney cancer incidence in hypertensive patients. Because elevated angiotensin II levels might contribute to carcinogenesis, we tested whether angiotensin II induces DNA damage in the kidney. In isolated perfused mouse kidneys, as little as 1 nmol/L angiotensin II caused a significant increase in DNA strand breaks, measured with the comet assay. This damage was independent of the hemodynamic effect of angiotensin II and mediated by the angiotensin II type 1 receptor. Angiotensin II also caused double-strand breaks in the cells of the isolated perfused kidney, detected with an antibody against the double-strand break marker γ-H2AX. Studies in cell culture allowed further characterization of the DNA damage induced by angiotensin II. Single- and double-strand breaks, abasic sites, and 7,8-dihydro-8-oxo-guanine, all types of oxidative DNA lesions, were detected in angiotensin II–treated renal cells. The majority of detected strand breaks was repaired within 1 hour, but double-strand breaks increased and persisted for at least 24 hours. [Cancer Res 2008;68(22):9239–46]
Ascorbic Acid-Induced Uricosuria
Authors: HOWARD B. STEIN
Journal: Annals of Internal Medicine (1976)

The effect of ascorbic acid on the serum and urinary uric acid was studied in 14 subjects. Two to 6 h after the ingestion of 4.0 g of ascorbic acid, the fractional clearance of uric acid increased to 202% +/- 41% of the control value. This uricosuria was inhibited by pyrazinamide and by low-dose acetylsalicylic acid, but was not accompanied by an increase of the creatinine clearnace. Ascorbic acid did not diminish protein-bound uric acid. In 3 subjects who ingested 8.0 g of ascorbic acid for 3 to 7 days the serum uric acid decreased by 1.2 to 3.1 mg/dl as a result of a sustained uricosuria. These results suggest that ascorbic acid could invalidate studies involving the measurement of uric acid and obscure the diagnosis of gout in some cases. Theoretically it could precipitate attacks of gouty arthritis or renal calculi in predisposed persons. These observations show a pharmacologic effect of megadoses of a simple vitamin.
BM-19 * SYMPTOMATIC AND ECONOMIC BURDEN OF BRAIN METASTASES IN PATIENTS WITH ALK+ NSCLC
Authors: A. Macalalad, M. Sasane, J. Zhang, K. Culver, K. Dea, R. Nitulescu, E. Wu, A. Guerin
Journal: Neuro-Oncology (2014)

BACKGROUND: Brain is one of the most common sites of metastasis in anaplastic lymphoma kinase positive (ALK+) locally advanced or metastatic non-small cell lung cancer (NSCLC). This study investigated symptoms and costs of ALK+ NSCLC patients before and after brain metastases (BM) as well as their treatment changes. METHODS: Retrospective data from 3 large US administrative databases (06/2011 to 06/2013) were evaluated. ALK+ NSCLC patients with BM were identified based on the use of crizotinib and diagnoses for secondary malignant brain tumors. Symptoms and costs were analyzed pre and post BM diagnosis (30 days before the first BM diagnosis). RESULTS: Among 213 ALK+ NSCLC patients with BM 70.4% had BM before initiating crizotinib, 19.2% were diagnosed with BM during crizotinib, and 10.3% after crizotinib. The frequency of BM-related symptoms post BM increased compared to pre BM, including fatigue (from 15% to 39%), headache (from 5% to 24%), depression (from 5% to 15%), altered mental status (from 1% to 13%), seizure (from 1% to 12%), stroke (from 0% to 10%), vision disorder (from 2% to 8%), drowsiness (from 0% to 6%), cognitive impairment (from 1% to 5%), and speech problems (from 0% to 4%). Average medical costs per patient per month were 5 times higher post BM compared to pre BM ($13,095 vs $2,517; p < .001), while pharmacy costs were more than 3 times higher post BM compared to pre BM ($7,213 vs $1,958; p < .001). The difference of medical costs was due to increases in inpatient costs ($6,677 vs $851) and outpatient costs ($5,863 vs $1,600), which were mainly related to radiotherapy or radiosurgery ($2,371 vs $410). CONCLUSIONS: BM presents a substantial symptomatic and economic burden in patients with ALK+ NSCLC. Given the large percentage of ALK+ NSCLC patients who will eventually develop BM, this highlights an important unmet need.
1048 A NOVEL HUMAN MONOCLONAL ANTIBODY DIRECTED AGAINST THE E2 GLYCOPROTEIN OF HEPATITIS C VIRUS (HCV) PREVENTS INFECTION IN CHIMPANZEES
Authors: B.M. Blair, T.J. Broering, G.J. Babcock, G. Szabo, R.W. Finberg, P.S. Cheslock, M. Knauber, B.A. Leav, R. Lanford, R.H. Purcell, D.M. Ambrosino, D.C. Molrine
Journal: Journal of Hepatology (2009)
The Role of the Lung Microbiome in Health and Disease. A National Heart, Lung, and Blood Institute Workshop Report
Authors: Yvonne J. Huang, Emily S. Charlson, Ronald G. Collman, Sandra Colombini-Hatch, Fernando D. Martinez, Robert M. Senior
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Study of the human lung microbiome in the context of pulmonary health and disease is an area of emerging research interest that is being driven by several contributing factors. These factors include increased recognition of the diversity of human-associated microbiota, their roles in health and in diseases associated with chronic inflammation, and advancements in technologies and tools that have facilitated such discoveries about the microbiota in organ systems outside of the lung. Therefore, the overarching goals of lung microbiome research are: to identify and characterize microbial populations associated with the respiratory tract and lungs; to understand their roles in lung health and disease; and, we hope, to allow the development of improved approaches for diagnosing and treating chronic respiratory diseases in which the microbiome has a role. Recent studies of the lung microbiome have yielded a number of interesting findings but also highlighted questions and challenges for researchers and clinicians. In December 2011, the National Heart, Lung, and Blood Institute convened a workshop to identify key issues and areas for further attention or development to advance research on the lung microbiome. Current knowledge and the state of research on the lung and related areas of human microbiome investigation were reviewed and discussed.
The contribution of acidosis to renal osteodystrophy
Authors: Principal discussant: David A. Bushinsky
Journal: Kidney International (1995)

A 5-year-old boy was admitted to the hospital 19 years ago for repair of primary hypospadias. The serum creatinine was 1.2 mg/dl; the BUN, 33 mg/dl; and the bicarbonate concentration, 23 mEq/liter. The creatinine clearance, determined from a 24-hour urine collection, was 75 mI/mm/I .73 m2. An intravenous pyelogram demonstrated a faint nephrogram on the right and no nephrogram on the left. Renal function was markedly diminished bilaterally with dysplastic pelvicalyceal systems and renal dysplasia affecting the left renal parenchyma more than the right. A voiding cystourethrogram demonstrated a distended and irregular bladder with massive bilateral reflux, distended calyces and pelves, and tortuous, dilated ureters. After voiding and standing, most of the contrast medium was drained from the upper collecting system; however, the bladder contained 500 ml of residual urine. A urologist advised against surgery because the patient had never had a urinary tract infection. Over the next several years, the patient's renal function progressively declined. Thirteen years ago, the serum creatinine was 3.9 mgldl; phosphate, 5.5 mgldl; calcium, 8.8 mg/dl; and bicarbonate, 22 mEq/liter. Aluminum hydroxide was administered, as was vitamin D. Six months later, the serum creatinine was 4.9 mgldl; phosphate, 6.1 mg/dl; calcium, 8.6 mg/dl; and bicarbonate, 20 mEq/liter. Oral sodium bicarbonate was given and the aluminum hydroxide was increased. In spite of marked increases in oral aluminum hydroxide and sodium bicarbonate, the serum phosphate level ranged from 5.2 to 7.4 mgldl (mean, 6.2 mg/dl over 2 years) and the bicarbonate ranged from 16 to 23 mEq/liter (mean, 20.7 mEq/liter) as the serum creatinine increased to 9.8 mg/dl over the next 18 months. Approximately ii years ago, peritoneal dialysis was begun. The patient was evaulated for transplantation at 3 major university centers, but each required that bilateral nephrectomy be performed prior to transplantation; the patient and his family refused. Nine years ago, the patient's mode
Antihypertensive Medication And Surgery
Authors: Ralph T. Geer
Journal: JAMA (1975)

To the Editor.—  The recent article by Perlroth and Hultgren (232:1279, 1975) is a thoughtful summary of problems faced in the care of the cardiac  during the perioperative period. However, we take issue with one point. They recommend discontinuing the use of antihypertensive medication in the usual hypertensive patient two weeks prior to surgery. This idea is an unfortunate relic from the time when neither the pharmacology of antihypertensives nor their interaction with anesthetics was well understood. Despite data to the contrary, 1 at least one well-known cardiology text supports routine discontinuance of the use of antihypertensive agents for as long as two weeks prior to surgery. 2 We believe this view is unwarranted. Untreated hypertensive patients and those with poorly controlled hypertension have alarming and poorly tolerated swings in blood pressure during anesthesia and surgery and in the immediate postoperative period. There is an increased incidence of myocardial
Hierarchical Structure of Electrospun Composite Fibers for Long‐Term Controlled Drug Release Carriers
Authors: Changmin Hu, Wenguo Cui
Journal: Advanced Healthcare Materials (2012)

A novel hierarchical structure of electrospun composite fibrous scaffolds is fabricated for long-term controlled drug release carriers. The low initial burst and long-term (more than 100 days) drug release of the composite fibrous scaffolds are due to the hierarchical structure and hydrophobicity of the composite fibers. Detailed facts of importance to specialist readers are published as "Supporting Information". Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.