tbuckley/cabot-search huggingface dataset:
Propranolol Antagonizes the Anti-Inflammatory Effect of Alcohol and Improves Survival of Infected Intoxicated Rabbits
Authors: R. Michael Buckley, Elvira S. Ventura, Rob Roy MacGregor
Journal: Journal of Clinical Investigation (1978)

We studied the effects of alcohol and propranolol on the course of peritonitis in rabbits. Induction of sterile peritonitis with normal saline led to a 50% augmentation of granulocyte adherence in normal rabbits, and a mean cumulative granulocyte count of 27,000/mm(3) in peritoneal exudate by 8 h. Rabbits intoxicated with alcohol at the time of peritonitis induction maintained a granulocyte adherence below pretreatment values, and only delivered a cumulative mean of 12,000 granulocytes/mm(3) into the peritoneal fluid. When intoxicated rabbits received propranolol intravenously at the time of intoxication, adherence increased above preperitonitis levels, and stayed significantly above values for animals given alcohol alone. In addition, the defect in granulocyte delivery was prevented by propranolol, resulting in a mean cumulative granulocyte count in peritoneal fluid of 24,000/mm(3).When peritonitis was induced with live pneumococci instead of a sterile inflammatory stimulus, 14/18 normal animals survived the infection and were culture-negative when sacrificed at 2 wk. In contrast, 17/18 intoxicated animals died of the infection, in a mean of 2.8 days. 9 of 18 intoxicated animals who also received propranolol survived, and those who died lived a mean of 7.5 days. The survival rates and the time-to-death among the nonsurvivors given propranolol were both significantly greater than in the animals intoxicated without propranolol. Thus, propranolol prevents the granulocyte adherence and delivery defects induced by alcohol intoxication, and significantly improves survival from infection.
Congenital or Early Developmental Versus Later Acquired Renal Function Asymmetry Scintigraphic Characteristics
Authors: MARKUS A. WHITLEY, ARNOLD F. JACOBSON
Journal: Clinical Nuclear Medicine (1993)

A congenitally or developmentally small right kidney in an adult spinal cord injury patient had only 12% of total uptake on radioiodine-labeled orthoiodohippurate renography but nevertheless had a normal-shaped time-activity curve. In a subsequent retrospective review of 175 consecutive radioiodine-labeled ortholodohippurate renograms performed on adult patients over a 3-years period, 35 other patients with studies showing greater than 2:1 asymmetry in renal function were identified. Uptake, clearance or both were abnormal in all 35 kidneys with less than 33.3% of function, with the left kidney more commonly affected (N = 24). Correlation from ultrasound, computerized tomography, intravenous pyelography, and angiography demonstrated acquired abnormalities associated with all 35 of these kidneys, including urinary obstruction (n = 20), renal artery stenosis (n = 9), and cortical scarring/Infection and/or reflux (N = 15) (some patients had more than one diagnosis). While acquired renal function asymmetry almost always results in a smaller kidney with abnormal uptake or clearance characteristics, a congenitally small kidney may have overall reduced blood flow but still display a normal-shaped time-activity curve on radionuclide renography.
Deficiency of coagulation factor XIII A subunit caused by the dinucleotide deletion at the 5' end of exon III.
Authors: T Kamura, T Okamura, M Murakawa, H Tsuda, T Teshima, T Shibuya, M Harada, Y Niho
Journal: Journal of Clinical Investigation (1992)

A congenital deficiency of the coagulation Factor XIII A subunit (F XIII A) is a rare autosomal recessive disorder that is characterized by a life-long bleeding tendency complicated by a difficulty in healing. Thus far, no molecular genetic analysis of this disorder has been reported. In this study, we demonstrate the molecular abnormalities in a family with this disorder. We performed Northern blot analysis of peripheral blood monocytes obtained from the propositus and found a 4-kb single band of F XIII A mRNA whose size was identical with that of normal subjects. Exons II-XV, which encode all the amino acids, were individually amplified by a polymerase chain reaction (PCR). All PCR products from the propositus had lengths indistinguishable from those of the wild type on agarose gel, suggesting that this defect results from either a point mutation or a short deletion/insertion. The sequencing of F XIII A cDNA from the propositus revealed a deletion of the dinucleotide AG within the AGAG repeat at the position of 210 to 213. Concerning the genomic sequence, a deletion of dinucleotide AG was also demonstrated in the intron B-exon III boundary. This deletion appeared to cause a frameshift mutation making a new stop codon shortly thereafter, and leading to a deficiency of plasma F XIII A. The heterozygosity of the F XIII A deficiency in the patient's offspring was documented by the nucleotide sequences of their exon III.
Abstract B50: A new class of diazonamide analogs with improved antitumor activity
Authors: Lin Li, Qi Wei, Ming Zhou, Vijayashree Ramesh, Xiaodong Wang, Patrick G. Harran, Lai Wang
Journal: Clinical Cancer Research (2010)

Abstract Diazonamide A is a natural product originally isolated from a marine organism. It potently induces G2/M cell cycle arrest. Its molecular mode of action is not fully understood but its potential as a cancer therapeutic is high. We previously reported that AB5, a close analog of diazonamide A, exhibits potent anti-tumor activity in mouse xenograft models. Tumor regression occurs in the absence of systemic toxicity typical of anti-mitotic chemotherapy. Here we show for the first time that the natural diazonamide compound possesses strong tumor killing activity in vivo xenograft models. To streamline our diazonamide synthesis and to define a minimal pharmacophore, we prepared a series of truncated structures. One of these, JP1838, was found to be as potent as AB5. Its simplified structure and shortened synthesis allowed for extensive structure activity relationship analyses. Several modifications markedly improved activity. One analog, JP2295, is &amp;gt;20 fold more potent than AB5 in a MIA Paca-2 pancreatic cancer xenograft model. More importantly, in HPAC pancreatic cancer and HCT-116 colon cancer xenograft models, JP2295 demonstrates greater efficacy and less toxicity than docetaxel and vinorelbine. Safety studies were therefore carried out in NIH Swiss mice. At doses10-fold higher than required for strong efficacy, JP2295 does not exhibit toxicities common to docetaxel and vinorelbine treatments. These include body weight loss, neutropenia, and myelosuppression. Such a large therapeutic window is unique for a small molecule antimitotic and suggests further development is warranted. Citation Information: Clin Cancer Res 2010;16(14 Suppl):B50.
Serratia marcescens granuloma
Authors: T. Yanagi, K. Katagiri, T. Sonada, S. Takayasu
Journal: British Journal of Dermatology (1997)

Journal Article Serratia marcescens granuloma Get access T. Yanagi, T. Yanagi Department of Dermatology, Oita Medical University, 1–1 Idaigaoka, Hasama–machi, Oita 879–55, Japan Search for other works by this author on: Oxford Academic Google Scholar K. Katagiri, K. Katagiri Department of Dermatology, Oita Medical University, 1–1 Idaigaoka, Hasama–machi, Oita 879–55, Japan Search for other works by this author on: Oxford Academic Google Scholar T. Sonada, T. Sonada Department of Dermatology, Oita Medical University, 1–1 Idaigaoka, Hasama–machi, Oita 879–55, Japan Search for other works by this author on: Oxford Academic Google Scholar S. Takayasu S. Takayasu Department of Dermatology, Oita Medical University, 1–1 Idaigaoka, Hasama–machi, Oita 879–55, Japan Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 136, Issue 2, 1 February 1997, Pages 289–290, https://doi.org/10.1111/j.1365-2133.1997.tb14919.x Published: 01 February 1997
Phase I Clinical Trial of BMS-247550, A Derivative of Epothilone B, Using Accelerated Titration 2B Design
Authors: Shirish M. Gadgeel, Antoinette Wozniak, Ramesh R. Boinpally, Richard Wiegand, Lance K. Heilbrun, Vikas Jain, Ralph Parchment, Dimitrios Colevas, Marvin B. Cohen, Patricia M. LoRusso
Journal: Clinical Cancer Research (2005)

Abstract Purpose: BMS-247550 is a semisynthetic derivative of epothilone B with mechanism of action analogous to paclitaxel. It has shown impressive antitumor activity in preclinical studies including in taxane-resistant models. We conducted a phase I trial, based on accelerated titration “2B” design, of BMS-247550 given as a 1-hour infusion every 3 weeks. Experimental Design: Seventeen patients (M:F, 10:7; median age, 54 years; performance status, 0-2) were treated on the trial. Forty-five cycles (1-9 cycles) of BMS-247550 were given at dosages ranging from 7.4 to 56 mg/m2. All patients received prophylaxis for hypersensitivity reactions, related to Cremophor-EL, with steroids and histamine antagonists. Results: First-course dose-limiting toxicity (DLT) was observed in two of three patients at 56 mg/m2 (neutropenic sepsis, prolonged grade 4 neutropenia) and in one of six patients at 40 mg/m2. Nonhematologic grade 3 to 4 toxicities observed were emesis and fatigue and they occurred only at 56 mg/m2. Grade 1 to 2 peripheral neuropathy was also observed. Other grade 1 to 2 toxicities were myalgias, arthralgias, rash, hand/foot syndrome, and mucositis. AUC and Cmax seemed proportional to the dose and the DLT. Development of neutropenia with BMS-247550 is related to the duration of drug exposure above a threshold. Conclusions: The maximum tolerated dose (MTD) of BMS-247550 is 40 mg/m2 given every 3 weeks. Neutropenia is the DLT. The accelerated titration “2B” design may help in determining MTD with fewer patients enrolled and more being treated closer to the MTD. However, the accelerated titration design did not seem to shorten the study duration.
Doxorubicin-loaded porous PLGA microparticles with surface attached TRAIL for the inhalation treatment of metastatic lung cancer
Authors: Insoo Kim, Hyeong Jun Byeon, Tae Hyung Kim, Eun Seong Lee, Kyung Taek Oh, Beom Soo Shin, Kang Choon Lee, Yu Seok Youn
Journal: Biomaterials (2013)
Xpert MTB/RIF False Detection of Rifampin-Resistant Tuberculosis from Prior Infection
Authors: J. Daniel Kelly, Shou-Yean Grace Lin, Pennan M. Barry, Chris Keh, Julie Higashi, John Z. Metcalfe
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

A 71-year-old man with two prior episodes of pulmonary tuberculosis (TB) in China (2008China ( -2009) ) and San Francisco, California (2009-2010) presented in July 2013 with progressive shortness of breath.The patient immigrated to San Francisco in November 2008, at which time he was noted to have right upper lobe scarring with cavity formation (Figures 1A and1B); three sputa were smear-negative and culture-negative for acid-fast bacilli (AFB).In July 2009, the man developed right upper lobe (RUL) consolidation in the area of the previously noted cavitary lesion, as well as pleural effusion (Figure 1C).Pan-susceptible Mycobacterium tuberculosis complex (MTBC) was isolated from both sputum and pleural biopsy.The patient completed standard short-course TB treatment in March 2010, when follow-up chest radiograph demonstrated interval decrease of the 3 3 2 cm RUL opacity; three sputa were again smear-negative and culturenegative.Persistent RUL opacity was noted at 12-month posttreatment follow-up in 2011, although sputum cultures remained negative.The patient returned intermittently to China and declined 18-month follow-up.In July 2013, the patient presented to our emergency department with 2 days of progressive shortness of breath without fevers, night sweats, cough, or weight loss.Computed tomography showed bilateral pleural effusions and persistent RUL opacification (Figures 1D and1E).On hospital day 2, a sputum specimen sent for concentrated smear demonstrated few AFB.Xpert MTB/RIF (Cepheid, Sunnyvale, CA) testing of this specimen showed MTBC at very low quantity (mean cycle threshold, 30.6), with rifampin resistance detected within the region of probe A (see Figure E1 in the online supplement).On hospital day 3, rifampin, isoniazid, pyrazinamide, ethambutol, moxifloxacin, capreomycin, and linezolid were initiated pending confirmatory testing.Complete blood count was within normal limits, hemoglobin A1c level (15.7 mg/dL) indicated poorly controlled diabetes mellitus, HIV testing was negative, and blood cultures demonstrated no growth.The concentrated sputum specimen tested by Xpert was sent to the Microbial Diseases Laboratory of the California Department of Public Health for pyrosequencing (1).The molecular target of IS6110 for MTBC identification and six loci, including rpoB for drug resistance detection, yielded no sequences, implying insufficient DNA or no MTBC present.Repeat sputum smears were AFB-negative.Diagnostic thoracentesis demonstrated transudative pleural fluid and no AFB on smear examination.On hospital day 8, the specimen tested by Xpert became culture-positive, with morphology consistent with non-TB mycobacteria (NTM).Repeat pyrosequencing and Xpert testing from the broth culture (BacT/ALERT 3D system; bioMerieux Inc., Durham, NC) were
Dapsone in the treatment of miliary lupus of the face
Authors: K. KUMANO, M. TANI, Y. MURATA
Journal: British Journal of Dermatology (1983)

In an uncontrolled study of twelve patients with miliary lupus of the face, dapsone gave good therapeutic results. Miliary lupus of the face (MLF) is an asymptomatic papular eruption affecting the central area of the face, which runs a chronic course and involutes spontaneously with scarring. Histopathologically, the papules usually show scattered masses of tuberculoid granulomata composed of epithelioid cells, giant cells, and an encircling rim of small round mononuclear cells in the dermis. The actiology and pathogenesis of this condition are still unknown. The treatment of MLF has not been satisfactory despite the use of many topical and systemic agents. In this paper we report that dapsone has been found to be beneficial in the treatment of MLF and has accelerated its resolution in twelve patients.
Increased expression of neutrophil and monocyte adhesion molecules in unstable coronary artery disease.
Authors: A Mazzone, S De Servi, G Ricevuti, I Mazzucchelli, G Fossati, D Pasotti, E Bramucci, L Angoli, F Marsico, G Specchia
Journal: Circulation (1993)

BACKGROUND A rapid increase in leukocyte adhesion to endothelial cells is one of the first events in the acute inflammatory response and in the pathogenesis of vascular diseases. A subgroup of cell surface glycoproteins (the CD11/CD18 complex) play a major role in the leukocyte adhesion process; in particular, the CD11b/CD18 receptor can be upregulated severalfold in response to chemotactic factors. The purpose of this study was to assess whether upmodulation of granulocyte and monocyte CD11b/CD18 receptors takes place during the passage of blood through the coronary tree of patients with clinical manifestations of ischemic heart disease. METHODS AND RESULTS Thirty-nine patients who underwent diagnostic coronary arteriography were studied. Group 1 (15 patients) had a clinical diagnosis of unstable angina, group 2 (14 patients) had stable exertional angina, and group 3 (10 patients) had atypical chest pain. Simultaneous sampling from the coronary sinus and aorta was obtained before coronary arteriography. Cell surface receptors were detected by direct immunofluorescence evaluated by flow cytofluorimetry using monoclonal antibodies tagged with fluorescent markers. Leukocytes were stained in unseparated blood to avoid in vitro manipulation that could activate phagocytes. Group 1 and 2 patients had significant coronary artery disease (&gt; 50% coronary narrowing in at least one major coronary vessel), whereas group 3 patients had normal coronary arteries. In group 1, granulocytes and monocytes showed a significantly higher expression of the CD11b/CD18 adhesion receptor in the coronary sinus than in the aorta (both P &lt; .01), whereas no difference in CD11b/CD18 expression was seen in groups 2 and 3. CONCLUSIONS Patients with unstable angina have an increased expression of granulocyte and monocyte CD11b/CD18 adhesion receptors, indicating that an inflammatory reaction takes place within their coronary tree. Activation of these leukocytes may induce coronary vasoconstriction, favor thrombotic processes, and further activate platelets, thus having potential implications on the pathogenesis of unstable coronary artery disease.
The Retina: An Approachable Part of the Brain
Authors: John B. Selhorst
Journal: JAMA (1988)

As aptly suggested in the title, a study of neural processes operant in the retina should assist in an understanding of the intricate mechanisms involved in the workings of the brain. If this was the intent of this work, the goal has been accomplished. In sharing both his experience as a renowned investigator of the retina and the evolution of neurobiology in the past three decades, Dr Dowling presents a number of complex concepts involving neural mechanisms in the retina and leaves the reader to ponder parallels in the central nervous system. Thus, this book should appeal to all students and researchers in the field of neurobiology as well as clinicians with an interest in retinal physiology. For the nonspecialist, the prose is simple and clear, and an excellent primer chapter at the end of the text presents fundamental concepts and terms pertaining to recent research of the retina and
Platelet thrombospondin and glycoprotein IV abnormalities in patients with essential thrombocythemia: Effect of α‐interferon treatment
Authors: C. Legrand, S. Bellucci, M. Disdier, G. Tobelem, L. Edelman
Journal: American Journal of Hematology (1991)

Abstract Platelet aggregability and some biochemical parameters were evaluated in seven patients with essential thrombocythemia (ET) compared with seven patients with secondary thrombocytosis (ST). Defective platelet aggregation with one or more agonists was seen in five patients with ET whereas aggregation was increased in two other patients. In addition, three patients with ET demonstrated spontaneous platelet aggregation in citrated plasma. This was associated with increased level of thrombospondin (TSP) in the plasma membrane. Interestingly, the presence of a proteolyzed 160 kDa form of TSP was detected in all patients with ET, whereas it was never found in patients with ST. Furthermore, three patients with ET demonstrated increased levels of platelet surface glycoprotein IV (GP IV), the putative receptor for TSP in the plasma membrane. In two of these patients, this correlated with increased surface expression of TSP and spontaneous platelet aggregation. The results suggest a possible link between the increased number of plasma membrane GP IV molecules, the spontaneous expression of TSP on the platelet surface and platelet hyperaggregability in some ET patients. The levels of plasma membrane GP IV and platelet surface‐associated TSP tended to be normalized during α‐interferon treatment, whereas the presence of an altered form of TSP persisted. This last parameter might be of practical usefulness in the characterization of the disease, permitting a clear distinction from ST.
Rugby (the religion of Wales) and its influence on the Catholic church: should Pope Benedict XVI be worried?
Authors: G. C Payne, R. E Payne, D. M Farewell
Journal: BMJ (2008)

<b>Objective</b> To explore the perceived wisdom that papal mortality is related to the success of the Welsh rugby union team. <b>Design</b> Retrospective observational study of historical Vatican and sporting data. <b>Main outcome measure</b> Papal deaths between 1883 and the present day. <b>Results</b> There is no evidence of a link between papal deaths and any home nation grand slams (when one nation succeeds in beating all other competing teams in every match). There was, however, weak statistical evidence to support an association between Welsh performance and the number of papal deaths. <b>Conclusion</b> Given the dominant Welsh performances of 2008, the Vatican medical team should take special care of the pontiff this Christmas.
A comparative double blind study of ketoconazole and griseofulvin in dermatophytosis
Authors: R.J. HAY, Y.M. CLAYTON, W.A.D. GRIFFITHS, P.M. DOWD
Journal: British Journal of Dermatology (1985)

The merits of oral ketoconazole and griseofulvin in dermatophytosis have been compared in a double blind study on 74 patients with 152 infected sites. The initial daily doses were 200 mg and 500 mg respectively, but these were doubled after 3 months if there was an inadequate clinical response. Treatment was continued either until clinical and mycological remission was achieved or a year of therapy had been given. Seventy‐five percent (total 80) and 74% (total 72) of all infected sites treated with ketoconazole and griseofulvin respectively were cleared of infection. However, in toe nail infections the respective cure rates were only 21% and 17%. Ketoconazole appeared to act more rapidly in curing tinea corporis or tinea cruris due to Trichophyton rubrum, whereas griseofulvin was superior in T. interdigitale infections. No serious side‐effects were encountered in either treatment group. In view of the slight risk of drug‐induced hepatitis, ketoconazole is best reserved as a second‐line drug for toe nail infections unless there are specific indications, such as griseofulvin intolerance. In these cases liver function tests should be monitored regularly throughout therapy.
AstraZeneca to pay $198m to patients over diabetes claims
Authors: J. H. Tanne
Journal: BMJ (2010)

The US drug company AstraZeneca announced this month that it will pay out $198m (£127m; €155m) to 17 500 patients, most of whom claimed that the antipsychotic drug quetiapine fumarate (Seroquel) had caused them to develop diabetes.

The company has reached agreements in principle with attorneys representing patients, but the agreements have not yet been finalised. The specific terms of the agreement, which resulted from court ordered mediation, are confidential.

The company spokesperson Tony Jewell told the BMJ , “Plaintiffs generally …
Diagnosis and Management of Rheumatic Diseases
Authors: Thomas G. Benedek
Journal: JAMA (1989)

If you need an up-to-date reference on the rheumatic diseases, should you purchase this volume, which, in comparison with the 1989 edition ofArthritis and Allied Diseases, edited by D. J. McCarty, is half as long and contains two thirds as many illustrations at half the cost? Katz's aim was to provide a comprehensive approach that emphasizes how the patient presents clinically to the physician... [particularly] regional and systemic diagnosis, multidisciplinary management, psychosocial interactions....  The 101 authors, 15 of whom also wrote for McCarty, have largely achieved this goal. The arrangement of manifestations of various diseases by anatomic regions is convenient and excellent for teaching, but necessarily leads to duplication in the description of systemic diseases. However, the text is written clearly, and its conciseness is well supplemented by some relatively simple tables. Other tables and diagnostic algorithms are difficult to read because of their comprehensiveness. For instance, Differential Diagnosis