tbuckley/cabot-search huggingface dataset:
A National Survey of Physician–Industry Relationships
Authors: Eric G. Campbell, Russell L. Gruen, James Mountford, Lawrence G. Miller, Paul D. Cleary, David Blumenthal
Journal: New England Journal of Medicine (2007)

Relationships between physicians and pharmaceutical, medical device, and other medically related industries have received considerable attention in recent years. We surveyed physicians to collect information about their financial associations with industry and the factors that predict those associations.We conducted a national survey of 3167 physicians in six specialties (anesthesiology, cardiology, family practice, general surgery, internal medicine, and pediatrics) in late 2003 and early 2004. The raw response rate for this probability sample was 52%, and the weighted response rate was 58%.Most physicians (94%) reported some type of relationship with the pharmaceutical industry, and most of these relationships involved receiving food in the workplace (83%) or receiving drug samples (78%). More than one third of the respondents (35%) received reimbursement for costs associated with professional meetings or continuing medical education, and more than one quarter (28%) received payments for consulting, giving lectures, or enrolling patients in trials. Cardiologists were more than twice as likely as family practitioners to receive payments. Family practitioners met more frequently with industry representatives than did physicians in other specialties, and physicians in solo, two-person, or group practices met more frequently with industry representatives than did physicians practicing in hospitals and clinics.The results of this national survey indicate that relationships between physicians and industry are common and underscore the variation among such relationships according to specialty, practice type, and professional activities.
Five-Year Follow-Up After Intracoronary Gamma Radiation Therapy for In-Stent Restenosis
Authors: Ron Waksman, Andrew E. Ajani, R. Lawrence White, Rosanna Chan, Bill Bass, Augusto D. Pichard, Lowell F. Satler, Kenneth M. Kent, Rebecca Torguson, Regina Deible, Ellen Pinnow, Joseph Lindsay
Journal: Circulation (2004)

The Washington Radiation for In-Stent Restenosis Trial is a double-blinded randomized study evaluating the effects of intracoronary radiation therapy (IRT) in patients with in-stent restenosis (ISR).One hundred thirty patients with ISR (100 native coronary and 30 vein grafts) underwent percutaneous transluminal coronary angioplasty, laser ablation, rotational atherectomy, or additional stenting (36% of lesions). Patients were randomized to either 192-Iridium IRT or placebo, with a prescribed dose of 15 Gy to a 2-mm radial distance from the center of the source. Angiographic restenosis (27% versus 56%, P=0.002) and target vessel revascularization (26% versus 68%, P<0.001) were reduced at 6 months in patients treated with IRT. Between 6 and 60 months, patients treated with IRT compared with placebo had more target lesion revascularization (IRT, 21.6% versus placebo, 4.7%; P=0.04) and target vessel revascularization (IRT, 21.5% versus placebo, 6.1%; P=0.03). At 5 years, the major adverse cardiac event rate was significantly reduced with IRT (46.2% versus 69.2%, P=0.008).In the Washington Radiation for In-Stent Restenosis Trial, patients with ISR treated with IRT using 192-Iridium had a reduction in the need for repeat target lesion and vessel revascularization at 6 months and 5 years.
Gestational Exposure of Mice to Secondhand Cigarette Smoke Causes Bronchopulmonary Dysplasia Blocked by the Nicotinic Receptor Antagonist Mecamylamine
Authors: Shashi P. Singh, Sravanthi Gundavarapu, Kevin R. Smith, Hitendra S. Chand, Ali Imran Saeed, Neerad C. Mishra, Julie Hutt, Edward G. Barrett, Matloob Husain, Kevin S. Harrod, Raymond J. Langley, Mohan L. Sopori
Journal: Environmental Health Perspectives (2013)

Cigarette smoke (CS) exposure during gestation may increase the risk of bronchopulmonary dysplasia (BPD)-a developmental lung condition primarily seen in neonates that is characterized by hypoalveolarization, decreased angiogenesis, and diminished surfactant protein production and may increase the risk of chronic obstructive pulmonary disease.We investigated whether gestational exposure to secondhand CS (SS) induced BPD and sought to ascertain the role of nicotinic acetylcholine receptors (nAChRs) in this response.We exposed BALB/c and C57BL/6 mice to filtered air (control) or SS throughout the gestation period or postnatally up to 10 weeks. Lungs were examined at 7 days, 10 weeks, and 8 months after birth.Gestational but not postnatal exposure to SS caused a typical BPD-like condition: suppressed angiogenesis [decreased vascular endothelial growth factor (VEGF), VEGF receptor, and CD34/CD31 (hematopoietic progenitor cell marker/endothelial cell marker)], irreversible hypoalveolarization, and significantly decreased levels of Clara cells, Clara cell secretory protein, and surfactant proteins B and C, without affecting airway ciliated cells. Importantly, concomitant exposure to SS and the nAChR antagonist mecamylamine during gestation blocked the development of BPD.Gestational exposure to SS irreversibly disrupts lung development leading to a BPD-like condition with hypoalveolarization, decreased angiogenesis, and diminished lung secretory function. Nicotinic receptors are critical in the induction of gestational SS-induced BPD, and the use of nAChR antagonists during pregnancy may block CS-induced BPD.
Enuresis, Epilepsy, and the Electroencephalogram
Authors: ALVIN F. POUSSAINT, RONALD B. KOEGLER, JEAN-LOUIS R. RIEHL
Journal: American Journal of Psychiatry (1967)

In a survey of 138 enuretic children it was found that none gave a history of seizures. EEGs were obtained on 68 consecutive children and seven (10 percent) were reported as abnormal, which is similar to the incidence of abnormal EEGs found among the general population. The results of our study do not support the hypothesis that enuresis is an "epileptic equivalent."
HLA-DP does not contribute towards susceptibility to systemic lupus erythematosus.
Authors: E J Davies, C J Hutchings, M C Hillarby, R P Donn, R G Cooper, E M Hay, R M Bernstein, P J Holt, D M Grennan, W E Ollier
Journal: Annals of the Rheumatic Diseases (1994)

OBJECTIVES--To determine whether HLA-DP genes are involved in determining susceptibility to systemic lupus erythematosus (SLE). METHODS--HLA-DPA1 and DPB1 genes were amplified by PCR of DNA samples from a panel of patients with SLE and normal controls. Amplified DNA was blotted on to nylon filters and probed with sequence-specific oligonucleotide (SSO) probes. RESULTS--No DPA1 or DPB1 allele was significantly associated with SLE, or with any immunological or clinical subset of SLE. Evidence was found for only limited linkage disequilibrium between HLA-DP and HLA-DQ/DR variants, and none between HLA-DP and the TAP2 gene. CONCLUSIONS--These data indicate that HLA-DP genes do not contribute towards determining susceptibility to SLE.
Augmented Expression of Neuronal Nitric Oxide Synthase in the Atria Parasympathetically Decreases Heart Rate During Acute Myocardial Infarction in Rats
Authors: Yoshihito Takimoto, Takeshi Aoyama, Koichi Tanaka, Reiko Keyamura, Yoshiki Yui, Shigetake Sasayama
Journal: Circulation (2002)

Background — Nitric oxide (NO) synthesized within sinoatrial cells recently has been shown to participate in the autonomic control of heart rate. We hypothesized that NO in the neuronal cells in the heart was increased and parasympathetically regulated heart rate after myocardial infarction (MI). Methods and Results — We examined heart rate dynamics and neuronal NO synthase (nNOS) expression and activities in the atria of rats with MI 1, 3, 7, and 14 days after MI (n=7 to 22 for each group). Both the mRNA levels of nNOS in the atria determined by competitive reverse transcriptase-polymerase chain reaction and the protein levels determined by Western blotting were significantly increased compared with controls 1, 3, and 7 days after MI. nNOS activity in the atria 1 day after infarction was also increased in MI rats. nNOS immunoreactivity was observed in nerve fibers in the atria. After infusion of a specific inhibitor of nNOS and iNOS, 1-(2-trifluoromethylphenyl) imidazole (TRIM) (50 mg/kg IV), heart rate was significantly ( P &lt;0.01) increased in MI rats compared with controls 1, 3, and 7 days after MI. The iNOS-specific inhibitor, 1400W (10 mg/kg SC), did not significantly affect the heart rate in rats with MI. The effect of TRIM was abolished by pretreatment with l -arginine (25 mg/kg IV) or by parasympathetic blockade with atropine but not by propranolol. There was a strong correlation ( r =0.837, P &lt;0.0001) between the nNOS protein expression and heart rate change after TRIM infusion. Conclusions — These results indicate that increased nNOS parasympathetically decreased heart rate via the production of NO in rats with acute MI.
Cardiac-Specific Overexpression of Inducible Nitric Oxide Synthase Does Not Result in Severe Cardiac Dysfunction
Authors: Jacqueline Heger, Axel Gödecke, Ulrich Flögel, Marc W. Merx, Andrei Molojavyi, W. Nikolaus Kühn-Velten, Jürgen Schrader
Journal: Circulation Research (2002)

Nitric oxide (NO), a potent regulator of myocardial contractility, has been implicated in the development of heart failure; however, no study exists describing the relation between expression of inducible nitric oxide synthase (iNOS), formation of NO in vivo, and cardiac contractility. We have therefore generated transgenic (TG) mice overexpressing iNOS under the cardiospecific α-myosin heavy chain (α-MHC) promoter. In vitro, iNOS activity in hearts of two transgenic lines was 260- to 400-fold above controls (wild type [WT]), but TG mice were viable and appeared normal. Ventricular mass/body weight ratio did not differ; heart rate and cardiac output as well as mean arterial blood pressure were decreased by 10%. NO x levels of hearts and blood of TG mice were 2.5- and 2-fold above WT controls, respectively. In the isolated heart, release of the NO oxidation products nitrate and nitrite, an index of in vivo NOS activity, was 40-fold over WT. However, cardiac hemodynamics and levels of ATP and phosphocreatine were unaltered. The high iNOS activity was associated with reduced cardiac l -arginine in TG hearts to only 15% of the WT, indicating limited substrate availability, whereas l -citrulline was 20-fold elevated. Our findings demonstrate that the heart can tolerate high levels of iNOS activity without detrimental functional consequences. The concept that iNOS-derived NO is the triggering factor in the pathomechanism leading to heart failure therefore needs to be reevaluated.
Immunotherapy for metastatic renal cell carcinoma: is it a therapeutic option yet?
Authors: M Guida, G Colucci
Journal: Annals of Oncology (2007)

Until 1 year ago, immunotherapy was considered the standard treatment of metastatic renal cell carcinoma (MRCC) producing objective response of 10%-20% and an overall survival of approximately 1 year. Recently, some multitarget-oriented drugs have shown an impressive activity in MRCC with a high percentage of partial response and/or stable disease with a significant impact on survival. Nevertheless, immunotherapy remains another important therapeutic option for these patients. The value of immunotherapy is its curative potential in some patients and its capability to obtain very durable responses as demonstrated by long-term follow-up. Interesting results seem obtained also when immunotherapy is used in combination with some chemotherapeutic agents. Gemcitabine demonstrated be a good drug to combine with immunotherapy because of its little detrimental effects on cellular immunity. In phase II studies, interesting results have been reported. We treated 41 patients with MRCC using a biweekly schedule including s.c. interleukin 2 (IL-2), gemcitabine and vinorelbine. The overall response was 40% and the median survival was 24 months. Treatment was well tolerated and easily manageable. Vaccines are another promising treatment of RCC intended to stimulate a specific antineoplastic response. Vaccines have been explored both in an adjuvant and in a metastatic setting. We started a pilot study with dendritic cells vaccine loaded with autologous tumor in MRCC. The treatment has resulted feasible, well tolerated and effective in a minority of patients. In the future, combination immunotherapy with multitarget-oriented drugs may be one way forward. Also advances in cellular therapies and new immunomodulatory molecules as monoclonal antibodies are producing new therapeutic options. Finally, the identification of a panel of prognostic factors could provide an important tool to guide the choice of treatment of patients with a different risk profile. Therefore, the increasing therapeutic options for RCC should be seen not as a competition among the different treatments but as an expanding armamentarium available for these patients.
Frontiers in Nephrology
Authors: Jörn Tongers, Douglas W. Losordo
Journal: Journal of the American Society of Nephrology (2007)

Cardiovascular-renal diseases are the leading causes of death and disability in the modern world. Moreover, chronic heart failure after myocardial infarction and peripheral arterial disease are predominant, devastating cardiovascular entities that limit prognosis and greatly impair quality of life in patients despite modern medical treatments. Cardiovascular diseases are also the predominant cause of death in people with renal diseases, underscoring the close relationship between these diseases. Until recently, medical efforts aimed only at prevention and slowing of functional deterioration after organ damage; however, the recent discovery of endogenous repair mechanisms involving hematopoietic stem and other progenitor cells has challenged the long-standing dogma regarding the inability to repair or regenerate terminally differentiated organs. A variety of stem and progenitor cell populations have shown properties that are potentially suited for tissue repair. After encouraging results in preclinical animal models, early clinical studies of endothelial progenitor cells (EPC) have begun. Envisioning the goal of true tissue regeneration, application of bone marrow-derived progenitors for heart and limb ischemia has provided early evidence of safety and feasibility. These studies have provided data indicating functional improvement as well. Although there is strong experimental and clinical evidence for a regenerative function of EPC even in renal disease, there has been no clinical application of this approach. After the initial flurry of activity, it is time to reconsider these approaches and attempt to optimize functional improvement and patient safety. This article briefly recapitulates biologic and functional characteristics of EPC before giving a concise overview on current therapeutic EPC applications in the field of cardiovascular-renal medicine with consideration of future challenges.
Reply to P. Autier et al
Authors: Adèle C. Green, Gail M. Williams
Journal: Journal of Clinical Oncology (2011)

Our article addressed the question of whether sunscreen, when used as a sun-protection agent, can prevent melanoma. It was emphasized that we view sunscreen as an adjunct means of sun protection when outdoors, in the context of use of other sun-protection measures such as wearing clothing, and seeking shade. The basic premise of our study therefore was that regular sunscreen is being used by people who are seeking to protect their skin from the effects of high sun exposure. In their letter, Autier et al convert our fundamental premise to: regular sunscreenusebypeoplewhoareactively seekingtheskineffectsof high sun exposure. Autier et al then ask whether our observed results mightnotapplytopeoplewhoareseekingratherthanmitigatinghighsun exposure?Oursummaryresponsewouldseemtostate theobvious—that increasedmelanomarisk inrelationtoregularsunscreenuse is influenced by the behavioral patterns of the sunscreen users rather than any direct effect of sunscreens.
Sleep Architecture and Respiratory Disturbances in Children with Obstructive Sleep Apnea
Authors: DANIEL Y. T. GOH, PATRICIA GALSTER, CAROLE L. MARCUS
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Little is known regarding sleep architecture in children with the obstructive sleep apnea syndrome (OSAS). We hypothesized that sleep architecture was normal, and that apnea increased over the course of the night, in children with OSAS. We analyzed polysomnographic studies from 20 children with OSAS and 10 control subjects. Sleep architecture was similar between the groups. Of obstructive apneas 55% occurred during rapid eye movement (REM) sleep. The apnea index, apnea duration, and degree of desaturation were greater during REM than non-REM sleep. OSAS data from the first and third periods of the night (periods A and C) were compared. Both the overall and the REM apnea index increased between periods A and C (11 to 25/h, p < 0.02; and 24 to 51/h, p < 0.01, respectively). There was no difference in SaO2 over time. Spontaneous arousals, but not respiratory-related arousals, were more frequent during non-REM than REM sleep; these did not change from periods A to C. We conclude that children with OSAS have normal sleep stage distribution. OSAS is predominantly a REM phenomenon in children. Obstructive apnea worsens over the course of the night, independent of the changing amounts of REM sleep. We speculate that this increase in apnea severity may be secondary to upper airway muscle fatigue, changes in upper airway neuromotor control, or changes in REM density.
Rapid improvement of coagulopathy by all‐<i>trans</i> retinoic acid in acute promyelocytic leukemia
Authors: Yohko Kawai, Kiyoaki Watanabe, Masahiro Kizaki, Mitsuru Murata, Tetsuji Kamata, Hideo Uchida, Takanori Moriki, Kenji Yokoyama, Michihide Tokuhira, Hideaki Nakajima, Makoto Handa, Yasuo Ikeda
Journal: American Journal of Hematology (1994)

Treatment of acute promyelocytic leukemia (APL) patients with all-trans retinoic acid (ATRA) was associated with rapid improvement in hemostatic markers. We made serial analyses of various hemostatic parameters in seven newly diagnosed APL patients. In all patients at diagnosis, plasma fibrinogen/fibrin degradation product (fragment-E), cross-linked fibrin degradation product (D-dimer fragment), thrombin-antithrombin III complex and plasmin-alpha 2-plasmin inhibitor complex were elevated, indicating the presence of disseminated intravascular coagulation (DIC). Antithrombin III (ATIII) levels were normal in all patients except for the patient with congenital ATIII deficiency. In four patients subsequently treated with ATRA without anticoagulant therapy, these hemostatic markers returned to near-normal levels by day 7 of treatment, indicating that DIC was essentially resolved. By contrast, in three patients who received conventional chemotherapy with a continuous low-dose heparin, improvement of coagulopathy was slower than in patients treated with ATRA. These results suggest that ATRA therapy exerts the rapid improvement in abnormal hemostatic markers in APL patients without any anticoagulant therapies, by inducing differentiation of leukemic cells and, in turns no massive release of procoagulant or fibrinolytic substances from these cells.
Descriptive epidemiology of bronchial reactivity in an adult population: results from a community study.
Authors: P G Burney, J R Britton, S Chinn, A E Tattersfield, A O Papacosta, M C Kelson, F Anderson, D R Corfield
Journal: Thorax (1987)

The bronchial response to inhaled histamine has been suggested as an epidemiological tool for assessing the prevalence of asthma, though the exact relationship between reactivity and asthma is unknown. Tests of bronchial reactivity to histamine were carried out in 511 subjects aged 18-64 years, randomly selected from the population in two areas of the South of England, who had returned questionnaires on respiratory symptoms. Bronchial reactivity to less than or equal to 8 mumol histamine was present in 14% and was associated with positive skin test responses to common allergens and with smoking history. Both of these relationships were in turn dependent on age, skin sensitivity being the more important determinant of reactivity in the young and smoking the more important in older subjects. Bronchial reactivity was least prevalent in the 35-44 year age group. No independent effect on reactivity of sex, social class, or area of residence was detected, and no significant effect from recent respiratory tract infections. Interpretation of the bronchial response to histamine in selected groups of subjects must take account of age, atopic state, and smoking history.
Alkaline phosphatase: placental and tissue-nonspecific isoenzymes hydrolyze phosphoethanolamine, inorganic pyrophosphate, and pyridoxal 5'-phosphate. Substrate accumulation in carriers of hypophosphatasia corrects during pregnancy.
Authors: M P Whyte, M Landt, L M Ryan, R A Mulivor, P S Henthorn, K N Fedde, J D Mahuren, S P Coburn
Journal: Journal of Clinical Investigation (1995)

Hypophosphatasia features selective deficiency of activity of the tissue-nonspecific (liver/bone/kidney) alkaline phosphatase (ALP) isoenzyme (TNSALP); placental and intestinal ALP isoenzyme (PALP and IALP, respectively) activity is not reduced. Three phosphocompounds (phosphoethanolamine [PEA], inorganic pyrophosphate [PPi], and pyridoxal 5'-phosphate [PLP]) accumulate endogenously and appear, therefore, to be natural substrates for TNSALP. Carriers for hypophosphatasia may have decreased serum ALP activity and elevated substrate levels. To test whether human PALP and TNSALP are physiologically active toward the same substrates, we studied PEA, PPi, and PLP levels during and after pregnancy in three women who are carriers for hypophosphatasia. Hypophosphatasemia corrected during the third trimester because of PALP in maternal blood. Blood or urine concentrations of PEA, PPi, and PLP diminished substantially during that time. After childbirth, maternal circulating levels of PALP decreased, and PEA, PPi, and PLP levels abruptly increased. In serum, unremarkable concentrations of IALP and low levels of TNSALP did not change during the study period. We conclude that PALP, like TNSALP, is physiologically active toward PEA, PPi, and PLP in humans. We speculate from molecular/crystallographic information, indicating significant similarity of structure of the substrate-binding site of ALPs throughout nature, that all ALP isoenzymes recognize these same three phosphocompound substrates.