tbuckley/cabot-search huggingface dataset:
Renal Tubular Acidosis Due to Amphotericin B
Authors: Donna Kern McCurdy, Myron Frederic, J. Russell Elkinton
Journal: New England Journal of Medicine (1968)

Nephrotoxicity, the major complication of long-term therapy with amphotericin B, is attributed to drug-induced renal vasoconstriction plus a direct toxic action on renal tubules. Hypokalemia and hyposthenuria may precede azotemia; biopsy usually shows nephrocalcinosis. Since these features suggest renal tubular acidosis (RTA), urinary acid excretion was studied in seven patients with amphotericin nephropathy. The results were compared with findings in 25 normal controls, six patients with other forms of renal disease and six with RTA. Five of the patients on amphotericin B had defects in acid excretion characteristic of distal RTA. These defects could not be attributed to decreased glomerular filtration. A tubular defect in acid excretion, superimposed on an ischemic kidney, appears to underlie both the hypokalemia and the nephrocalcinosis characteristic of amphotericin nephropathy. Concomitant alkali therapy during prolonged amphotericin B administration might prove prophylactically useful.
A Polyphenylene Dendrimer Drug Transporter with Precisely Positioned Amphiphilic Surface Patches
Authors: René Stangenberg, Yuzhou Wu, Jana Hedrich, Dennis Kurzbach, Daniel Wehner, Gilbert Weidinger, Seah Ling Kuan, Malin Insa Jansen, Fedor Jelezko, Heiko J. Luhmann, Dariush Hinderberger, Tanja Weil, Klaus Müllen
Journal: Advanced Healthcare Materials (2014)

The design and synthesis of a polyphenylene dendrimer ( PPD 3 ) with discrete binding sites for lipophilic guest molecules and characteristic surface patterns is presented. Its semi‐rigidity in combination with a precise positioning of hydrophilic and hydrophobic groups at the periphery yields a refined architecture with lipophilic binding pockets that accommodate defined numbers of biologically relevant guest molecules such as fatty acids or the drug doxorubicin. The size, architecture, and surface textures allow to even penetrate brain endothelial cells that are a major component of the extremely tight blood–brain barrier. In addition, low to no toxicity is observed in in vivo studies using zebrafish embryos. The unique PPD scaffold allows the precise placement of functional groups in a given environment and offers a universal platform for designing drug transporters that closely mimic many features of proteins.
Incidence of IDDM During 1984–1986 in Population Aged &amp;lt;30 Yr: Residents of Turin, Italy
Authors: Graziella Bruno, Franco Merletti, Elisabetta Pisu, Guido Pastore, Claudio Marengo, Gianfranco Pagano
Journal: Diabetes Care (1990)

The goal of this study was to measure the incidence of insulin-dependentdiabetes mellitus (IDDM) during 1984–1986 in residents of Turin, Italy, aged &amp;lt;30 yr. The primary data source was the list of all subjects diagnosed with IDDM who attended diabetes clinics in Turin. Other data sources were the general register of death certificates, the list of hospital discharges, andthe computerized data base of insulin prescriptions. Eighty incident cases of IDDM were identified during the study in 1,130,284 person-yr for those &amp;lt;30 yr of age. Ageadjusted (world standard) incidence rates were 8.05, 8.10, and 6.96/100,000 in the age-groups 0–14, 0–19, and 0–29 yr, respectively. Estimated completeness of the primary data source compared with all other data sources was 91%, whereas the estimated completeness of ascertainment ofthe registry was 99%. Incidence rates of IDDM in northern Italy compare withthose of European countries with low-medium incidence. A population-based register is being established for the province of Turin (951,445 inhabitants aged 0–29 yr) for the collection of incident cases since 1984.
Phenylephrine-Induced Ca <sup>2+</sup> Oscillations in Canine Pulmonary Artery Smooth Muscle Cells
Authors: Hiroshi Hamada, Derek S. Damron, Sung Jin Hong, David R. Van Wagoner, Paul A. Murray
Journal: Circulation Research (1997)

Abstract Modulation of [Ca 2+ ] i in response to receptor activation is a critical determinant of vascular smooth muscle tone. In this study, we examined the effect of continuous stimulation of α 1 -adrenoceptors with phenylephrine (PE) on [Ca 2+ ] i in single pulmonary artery smooth muscle cells (PASMCs) cultured from explants of canine intrapulmonary artery. Fura 2–loaded PASMCs pretreated with propranolol (5 μmol/L) were continuously superfused with PE at 37°C on the stage of an inverted fluorescence microscope, and [Ca 2+ ] i was measured using a dual-wavelength spectrofluorometer. Resting values of [Ca 2+ ] i were 96±4 nmol/L. PE (10 μmol/L) stimulated oscillations in [Ca 2+ ] i at a frequency of 1.35±0.07/min, which reached a peak [Ca 2+ ] i of 650±26 nmol/L (n=69 cells). The oscillations lasted for &gt;30 minutes and were constant in amplitude and frequency. Both the amplitude and frequency of PE-induced [Ca 2+ ] i oscillations increased in a dose-dependent (3×10 −8 to 10 −4 mol/L) manner. Pretreatment with the α 1 -adrenoceptor antagonist prazosin (50 nmol/L) or removal of extracellular Ca 2+ abolished the repetitive [Ca 2+ ] i oscillations induced by PE. The voltage-operated Ca 2+ channel blockers nifedipine (1 μmol/L) and verapamil (1 μmol/L) had no effect on the [Ca 2+ ] i oscillations. In contrast, inhibition of phospholipase C with U73122 (10 −7 to 10 −5 mol/L) attenuated the oscillations in a dose-dependent fashion. The nonselective protein kinase inhibitor staurosporine (10 −9 to 10 −7 mol/L) had a minimal inhibitory effect on the oscillations. Caffeine (30 mmol/L) and thapsigargin (1 μmol/L) abolished the oscillations, whereas pretreatment with ryanodine (1 to 100 μmol/L) had no effect. In freshly dispersed PASMCs, PE (10 μmol/L) induced oscillations in [Ca 2+ ] i similar to those observed in cultured cells, and patch-clamp experiments revealed oscillations in membrane potential. These results indicate that PE induces [Ca 2+ ] i oscillations in PASMCs via stimulation of α 1 -adrenoceptors coupled to phospholipase C activation. Voltage-operated Ca 2+ channels and protein kinases are not required for the oscillations. The requirement for extracellular Ca 2+ and intracellular Ca 2+ stores indicates that both Ca 2+ influx and intracellular Ca 2+ release play a role in the maintenance of the oscillations.
Government clarifies long term NHS care
Authors: J Andrews
Journal: BMJ (1994)

EDITOR, - John Warden's report on the clarification of responsibilities for long term health care suggests that the government has come full circle.1 However, the draft guidance contains the serious proviso that the individual authorities (health and social services) throughout the country reach their own agreements about “local criteria for eligibility” - that is, who needs health authority care (free at the point of issue) …
814. Adenovirus-Mediated Gene Transfer Demonstrates That Pirin, a Transcription Factor Up-Regulated in the Bronchial Epithelium by Cigarette Smoke, Mediates Bronchial Epithelial Cell Apoptosis
Authors: Brian D. Gelbman, Adriana Heguy, Timothy P. O'Connor, Joseph Zabner, Ronald G. Crystal
Journal: Molecular Therapy (2005)

Top of pageAbstract
Gene expression profiling using Affymetrix microarray analysis of airway epithelium obtained by bronchoscopy on matched cohorts of 13 phenotypically normal smokers and 9 non-smokers was used to identify specific genes modulated by smoking. Among these, we observed up-regulation of pirin (3.1-fold, p 500-fold in pirin expression over endogenous mRNA levels. The effect of Ad-mediated overexpression of pirin in BEAS-2B cells was assessed by quantifying the number of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive cells, and the number of cytoplasmic nucleosomes by ELISA. After 48 hr, Ad-pirin infection was associated with increases in both the number of TUNEL positive cells (4.4-fold change above AdNull, an empty Ad vector, p<0.01) and cytoplasmic nucleosomes by ELISA (7.9-fold change above AdNull, p<0.01). These results are consistent with the concept that pirin overexpression leads to increased apoptosis in the airway epithelium, an observation that has implications for the pathogenesis of cigarette smoke-induced diseases of the airways. This study illustrates the paradigm of combining microarray analysis of human cells with Ad-mediated gene transfer to demonstrate the relevance of candidate genes that play a role in the pathogenesis of human disease.
Clinical and Epidemiologic Features of Primary HIV Infection
Authors: Timothy Schacker
Journal: Annals of Internal Medicine (1996)

Background: The acute clinical events surrounding the acquisition of human immunodeficiency virus (HIV) have not been well characterized. Objective: To further define the clinical and epidemiologic presentation of primary HIV infection. Design: Descriptive cohort study. Setting: University research clinic. Patients: 46 adults (43 men and 3 women) with primary HIV infection who enrolled in the study a median of 51 days after HIV seroconversion. Measurements: Documentation of recent HIV seroconversion. Standardized collection of demographic characteristics and sexual contact history, results of tests for HIV RNA, HIV culture, and T-cell subsets. Results: 41 of 46 patients (89%) developed an acute retroviral syndrome. Primary HIV infection was infrequently diagnosed at the initial medical encounter, even in persons enrolled in routine HIV screening programs. Median numbers of sexual partners 6 months and 1 month before acquisition of HIV were three and one, respectively; 21 patients (46%) reported having had only one partner in the month before seroconversion. Of the 12 patients who could identify the precise date of and activity leading to seroconversion, 4 reported having only oral-genital contact. Conclusions: Primary HIV infection causes a recognizable clinical syndrome that is often underdiagnosed, even in persons enrolled in a program of routine surveillance for HIV infection. Frequency of sexual contact and overall numbers of sexual partners in this group of homosexual men who acquired HIV were markedly lower than those seen a decade ago. Acquisition of HIV does occur, even in persons with relatively few sexual partners. Increased attention to oral-genital contact as a means of acquiring HIV appears to be warranted.
Selected Pregnancy and Delivery Outcomes After Exposure to Antidepressant Medication
Authors: Lori E. Ross, Sophie Grigoriadis, Lana Mamisashvili, Emily H. VonderPorten, Michael Roerecke, Jürgen Rehm, Cindy-Lee Dennis, Gideon Koren, Meir Steiner, Patricia Mousmanis, Amy Cheung
Journal: JAMA Psychiatry (2013)

Untreated depression during pregnancy has been associated with increased morbidity and mortality for both mother and child and, as such, optimal treatment strategies are required for this population.There are conflicting data regarding potential risks of prenatal antidepressant treatment.To determine whether prenatal antidepressant exposure is associated with risk for selected adverse pregnancy or delivery outcomes. DATA SOURCES MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature, PsycINFO, and the Cochrane Library were searched from their start dates to June 30, 2010. STUDY SELECTION English-language studies reporting outcomes associated with pharmacologic treatment during pregnancy were included. We reviewed 3074 abstracts, retrieved 735 articles, and included 23 studies in this meta-analysis.Study design, antidepressant exposure, adjustment for confounders, and study quality were extracted by 2 independent reviewers.There was no significant association between antidepressant medication exposure and spontaneous abortion (odds ratio [OR], 1.47; 95% CI, 0.99 to 2.17; P = .055). Gestational age and preterm delivery were statistically significantly associated with antidepressant exposure (mean difference [MD] [weeks], -0.45; 95% CI, -0.64 to -0.25; P < .001; and OR, 1.55; 95% CI, 1.38 to 1.74; P < .001, respectively), regardless of whether the comparison group consisted of all unexposed mothers or only depressed mothers without antidepressant exposure. Antidepressant exposure during pregnancy was significantly associated with lower birth weight (MD [grams], -74; 95% CI, -117 to -31; P = .001); when this comparison group was limited to depressed mothers without antidepressant exposure, there was no longer a significant association. Antidepressant exposure was significantly associated with lower Apgar scores at 1 and 5 minutes, regardless of whether the comparison group was all mothers or only those who were depressed during pregnancy but not exposed to antidepressants.Although statistically significant associations between antidepressant exposure and pregnancy and delivery outcomes were identified, group differences were small and scores in the exposed group were typically within the normal ranges, indicating the importance of considering clinical significance. Treatment decisions must weigh the effect of untreated maternal depression against the potential adverse effects of antidepressant exposure.
Competing interest bias in academic publications
Authors: Jocalyn Clark
Journal: Journal of the Royal Society of Medicine (2009)

We agree entirely with Richard Smith and colleagues that competing interests beyond the financial are important, and appreciate their contribution to the debate.1 As we state in our recent editorial,2 PLoS Medicine takes all potential competing interests seriously. We accept that financial competing interests are easier to define and judge, but our editorial also outlines our position that more leadership and better policy are needed in the area of non‐financial competing interests. These interests include the potential biases that may emanate from the public sector cultures in which many scientists and academics work. We look forward to the continued debate on the topic of competing interests and encourage readers to respond to our recent editorial and its recommendations on our website.
The Unsolved Problem: Obtaining Personal Health Care
Authors: Maurice B. Strauss
Journal: New England Journal of Medicine (1968)

Seventy years ago personal health care was a privilege; today, it is considered a right. Then the physician's premedical education was often limited to high school and may not have included even an internship after medical school. Only a few physicians were specialists; today, the overwhelming majority are college graduates who have engaged in prolonged postgraduate training and practice in specialized fields.The scarcity of good personal health care, first noted years ago in rural areas, and later in the core cities, is now the subject of complaint from the suburbs. Despite the magnificent facilities available for specialized procedures that . . .
Prognostic significance of Doppler measures of diastolic function in cardiac amyloidosis. A Doppler echocardiography study.
Authors: A L Klein, L K Hatle, C P Taliercio, J K Oh, R A Kyle, M A Gertz, K R Bailey, J B Seward, A J Tajik
Journal: Circulation (1991)

BACKGROUND We have previously characterized the left ventricular diastolic filling abnormalities in cardiac amyloidosis by Doppler methods. The various filling patterns were shown to be related to the degree of cardiac amyloid infiltration. The purpose of this study was to determine the value of Doppler diastolic filling variables for assessing prognosis in cardiac amyloidosis. METHODS AND RESULTS We performed pulsed-wave Doppler studies of the left ventricular inflow and obtained clinical follow-up data in 63 consecutive patients with biopsy-proven systemic amyloidosis. All patients had typical echocardiographic features of cardiac involvement. The patients were subdivided into two groups according to deceleration time: Group 1 (33 patients) had a deceleration time of 150 msec or less, indicative of restrictive physiology, and group 2 (30 patients) had a deceleration time of more than 150 msec. Of the 63 patients, 32 (51%) died during a mean follow-up period of 18 +/- 12 months. Of these deaths, 25 (78%) were cardiac deaths, and 19 of the 25 patients (76%) were from group 1. The 1-year probability of survival in group 1 was significantly less than that in group 2 (49% versus 92%, p less than 0.001). Bivariate analysis revealed that the combination of the Doppler variables of shortened deceleration time and increased early diastolic filling velocity to atrial filling velocity ratio were stronger predictors of cardiac death than were the two-dimensional echocardiographic variables of mean left ventricular wall thickness and fractional shortening. CONCLUSIONS Doppler-derived left ventricular diastolic filling variables are important predictors of survival in cardiac amyloidosis.
Allogeneic hematopoietic stem cell transplantation in thalassemia major: results of a reduced-toxicity conditioning regimen based on the use of treosulfan
Authors: Maria Ester Bernardo, Eugenia Piras, Adriana Vacca, Giovanna Giorgiani, Marco Zecca, Alice Bertaina, Daria Pagliara, Benedetta Contoli, Rita Maria Pinto, Giovanni Caocci, Angela Mastronuzzi, Giorgio La Nasa, Franco Locatelli
Journal: Blood (2012)
Antimicrobial effects of phototherapy and photochemotherapy in vivo and in vitro
Authors: M. YOSHIMURA, S. NAMURA, H. AKAMATSU, T. HORIO
Journal: British Journal of Dermatology (1996)

We investigated the antimicrobial effects of phototherapy and photochemotherapy in vivo and in vitro. First, Staphylococcus aureus samples were obtained using stamp agar medium from inflammatory lesions of 29 adult patients with atopic dermatitis before and after a single photochemotherapy. Therapy was oral PUVA (30 mg 8-methoxypsoralen, 8MOP plus 5J/cm2 UVA), topical PUVA (0.3% 8MOP plus 200 mJ/cm2 UVA) or UVB (80 mJ/cm2) irradiation. The number of S. aureus on the lesions was significantly reduced, even after a single treatment with all therapies. Reductions (mean +/- SD) were 69.3 +/- 26.9%, 76.3 +/- 31.3% and 83.8 +/- 18.5%, respectively. Secondly, we investigated the effect of PUVA (0.001% 8MOP plus 10, 20, 30, 40, or 50 mJ/cm2 UVA) and UVB (10, 30, 50, or 100 mJ/cm2) irradiation on the proliferation of S. aureus in vitro. PUVA and UVB treatment markedly inhibited the proliferation in a dose-dependent manner. These results seem to indicate the possibility that the antimicrobial effect of UV radiation contributes to successful photochemotherapy in patients with atopic dermatitis.
Hospital twinning in Europe.
Authors: T. Richards
Journal: BMJ (1992)

logical hypertrophy of memory on an individual speaks of this as an "it" and the individual as an "I."8There may be a most complex relation between such an "it" and an "I," and the "it" of Tourette's is far more complex, for it can draw, like a dream, on the entire range of instinctual and preconscious forces, which the conscious mind can then manipulate.Perhaps it is in some complex act of balance or negotia- tion-partly deferring to, partly mastering, the energy of Tourette's -that the most potent Tourettic creativities arise.9One also sees this in Tourettic athletes: Jim Eisenreich, a baseball player, and Chris Jackson, a basketball player, who do not so much suppress as use their Tourette's, its speed, its spontaneity, to their own advantage.And there is a Tourettic disc jockey in Iowa, whose language, off the air, is a tissue of profanities but who, once the "on air" sign appears, has no profanities, no excursions, only force and speed, the roller- coaster of Tourette's orchestrated and mastered.I know actors with Tourette's syndrome, who may be similarly distracted or fragmented by their Tourette's offstage but are, seemingly, Tourette free on stage-but "Tourette free" is not the right phrase, for what one sees is Tourette's organised and mastered, its force all coordinated in the act of performance.Some Tourettic actors speak here of the integrating power of a role or identity.One must not romanticise Tourette's, or any other disease, nor make a romantic equation of disease and creativity (as Thomas Mann so often seemed to do).Creativity is usually in a different realm from disease.But with a disorder like Tourette's syndrome, especially in its phantasmagoric form, one may have the rather rare situation ofa biological condition becoming creative or becoming an integral part of the identity and creativity of an individual.Whether this was the case with Mozart is unclear, but that it occurs among others, and often, is quite beyond question.
CARDIAC REMODELING AND DIASTOLIC DYSFUNCTION PRECEDE NON MI-RELATED HEART FAILURE IN HIGH-RISK HYPERTENSIVE PATIENTS: THE LIFE ECHO SUBSTUDY.
Authors: Marcello Chinali, Gerard P. Aurigemma, Peter M. Okin, Eva Gerdts, Kristian Wachtell, Sverre E. Kjeldsen, Stevo Julius, Bjö;rn Dahlö;f, Giovanni de Simone, Richard B. Devereux
Journal: Journal of the American College of Cardiology (2010)
Histological changes in naevi with superimposed psoriasis
Authors: G. Fabrizi, G. Massi
Journal: British Journal of Dermatology (2000)

Journal Article Histological changes in naevi with superimposed psoriasis Get access G. Fabrizi, G. Fabrizi Departments of Dermatology and Search for other works by this author on: Oxford Academic Google Scholar G. Massi G. Massi Pathology, Catholic University School of Medicine, Largo F. Vito, 1, 00168 Rome, Italy Correspondence: Guido Massi, MDE‐mail: guidomassi@tiscalinet.it Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 143, Issue 3, 1 September 2000, Pages 688–690, https://doi.org/10.1111/j.1365-2133.2000.03818.x Published: 01 September 2000