tbuckley/cabot-search huggingface dataset:
Plasticity of Central Chemoreceptors: Effect of Bilateral Carotid Body Resection on Central CO2 Sensitivity
Authors: Albert Dahan, Diederik Nieuwenhuijs, Luc Teppema
Journal: PLoS Medicine (2007)

Human breathing is regulated by feedback and feed-forward control mechanisms, allowing a strict matching between metabolic needs and the uptake of oxygen in the lungs. The most important control mechanism, the metabolic ventilatory control system, is fine-tuned by two sets of chemoreceptors, the peripheral chemoreceptors in the carotid bodies (located in the bifurcation of the common carotid arteries) and the central CO2 chemoreceptors in the ventral medulla. Animal data indicate that resection of the carotid bodies results, apart from the loss of the peripheral chemoreceptors, in reduced activity of the central CO2 sensors. We assessed the acute and chronic effect of carotid body resection in three humans who underwent bilateral carotid body resection (bCBR) after developing carotid body tumors.The three patients (two men, one woman) were suffering from a hereditary form of carotid body tumors. They were studied prior to surgery and at regular intervals for 2-4 y following bCBR. We obtained inspired minute ventilation (Vi) responses to hypoxia and CO2. The Vi-CO2 responses were separated into a peripheral (fast) response and a central (slow) response with a two-compartment model of the ventilatory control system. Following surgery the ventilatory CO2 sensitivity of the peripheral chemoreceptors and the hypoxic responses were not different from zero or below 10% of preoperative values. The ventilatory CO2 sensitivity of the central chemoreceptors decreased by about 75% after surgery, with peak reduction occurring between 3 and 6 mo postoperatively. This was followed by a slow return to values close to preoperative values within 2 y. During this slow return, the Vi-CO2 response shifted slowly to the right by about 8 mm Hg.The reduction in central Vi-CO2 sensitivity after the loss of the carotid bodies suggests that the carotid bodies exert a tonic drive or tonic facilitation on the output of the central chemoreceptors that is lost upon their resection. The observed return of the central CO2 sensitivity is clear evidence for central plasticity within the ventilatory control system. Our data, although of limited sample size, indicate that the response mechanisms of the ventilatory control system are not static but depend on afferent input and exhibit a large degree of restoration or plasticity. In addition, the permanent absence of the breathing response to hypoxia after bCBR may aggravate the pathological consequences of sleep-disordered breathing.
Evolution of disability in coalworkers' pneumoconiosis.
Authors: J P Lyons, H Campbell
Journal: Thorax (1976)

Retrospective analysis of the results of serial ventilatory capacity tests (FEV 1-0), which had extended over an average period of almost 15 years, has been carried out in 215 miners and ex-miners who suffer with coalworkers' pneumoconiosis. All were unselected previously diagnosed cases who attend the Cardiff Pneumoconiosis Panel at regular intervals for re-assessment examinations. They consisted of 68 miners and 147 ex-miners and they were divided into three groups according to their radiological category at their most recent examination, carried out in either 1973 or 1974. There were 90 cases of category B progressive massive fibrosis (PMF), 50 cases of category A PMF and 75 cases of simple pneumoconiosis. Findings for the 38 life-long non-smokers within the 215 were compared with those for the smokers. All three groups showed progressive impairment of ventilation over the whole period of observation. This was most marked in the category B cases but this group had already acquired a substantial proportion of their eventual impairment while still classified radiologically as category A or as simple pneumoconiosis. These findings are not compatible with the view that coalworkers' pneumoconiosis does not cause significant impairment of ventilation until the category B radiological stage is attained; they suggest rather that cases destined to progress to serious disablement show evidence of progressive impairment of ventilation at very much earlier radiological stages. Non-smokers showed a pattern of impairment similar to that of the smokers but were less disabled; the differences, however, were slight and not statistically significant.
Age-related factors in cyclosporine-induced syngeneic graft-versus-host disease: regulatory role of marrow-derived T lymphocytes.
Authors: A C Fischer, A D Hess
Journal: The Journal of Experimental Medicine (1990)

The present studies have evaluated the effect of age on the induction of syngeneic graft-versus-host disease (SGVHD) after syngeneic bone marrow transplantation (BMT) and cyclosporine (CsA) therapy. The results clearly document an inverse correlation of age with the incidence of SGVHD. Virtually a 100% incidence of SGVHD occurs in Lewis rats when syngeneic BMT and CsA therapy are started when the animals are 4 wk of age. Thereafter, there is a dramatic decline in the incidence of SGVHD with the increasing age of the animals. Although the age of the recipient was important, the most significant effect was the age of the marrow donor. Marrow from animals 6 mo of age was virtually incapable of eliciting SGVHD after BMT and CsA therapy. Furthermore, mixing the marrow from mature and immature animals resulted in a decreased incidence of SGVHD, implicating a regulatory effect present in the marrow from older rats. This regulatory effect was due to the presence of mature T cells in the marrow from animals 6 mo of age. Despite the fact that marrow from young animals possesses mature T lymphocytes, this regulatory activity was absent, suggesting that the host resistance mediated by T lymphocytes develops as the animal ages. These data further implicate the importance of a host resistance mechanism in preventing the induction of SGVHD with CsA, which appears to be mediated by the clonal inactivation of autoreactive cells.
Phase I Trial of the Pan-PI3K Inhibitor Pilaralisib (SAR245408/XL147) in Patients with Chronic Lymphocytic Leukemia (CLL) or Relapsed/Refractory Lymphoma
Authors: Jennifer R. Brown, Matthew S. Davids, Jordi Rodon, Pau Abrisqueta, Siddha N. Kasar, Joanne Lager, Jason Jiang, Coumaran Egile, Farrukh T. Awan
Journal: Clinical Cancer Research (2015)

This phase I expansion-cohort study evaluated the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of the pan-PI3K inhibitor pilaralisib (SAR245408/XL147) in patients with chronic lymphocytic leukemia (CLL) or relapsed or refractory lymphoma.Patients were treated with the maximum tolerated dose of pilaralisib previously determined in patients with solid tumors (600 mg capsules once daily). Adverse events (AE) and response were evaluated. Plasma pharmacokinetics and pharmacodynamic effects on cytokines and chemokines were also assessed.Twenty-five patients were included in the study: 10 with CLL and 15 with lymphoma. The most frequent AEs of any grade were diarrhea (92.0%), pyrexia (52.0%), and fatigue (44.0%). The most frequent grade ≥3 AEs were neutropenia (32.0%), diarrhea (20.0%), and anemia (16.0%). Pilaralisib exposure on cycle 1 day 28 was similar to exposure in patients with solid tumors. In patients with CLL, pilaralisib significantly reduced plasma levels of several cytokines and chemokines involved in B-cell trafficking. Five patients (50.0%) with CLL and 3 patients (20.0%) with lymphoma had a partial response. Six patients (60.0%) with CLL had nodal shrinkage ≥50%. Overall, 14 patients (56.0%; 7 patients with CLL and 7 patients with lymphoma) had progression-free survival ≥6 months.Pilaralisib demonstrated an acceptable safety profile in patients with CLL and lymphoma, generally consistent with findings in patients with solid tumors. Single-agent pilaralisib showed preliminary clinical activity in patients with CLL and lymphoma, supporting further development.
Methylphenidate vs Atomoxetine: Personalized Medicine in Attention- Deficit/Hyperactivity Disorder
Authors: Hartmut Heinrich, Petra Studer, Gunther H. Moll, Oliver Kratz
Journal: JAMA Psychiatry (2013)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Psychiatry HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Psychiatry journal
Efficacy Differences of Pemetrexed by Histology in Pretreated Patients with Stage IIIB/IV Non-small Cell Lung Cancer: Review of Results from an Open-Label Randomized Phase II Study
Authors: Kaoru Kubota, Seiji Niho, Sotaro Enatsu, Yoshihiro Nambu, Yutaka Nishiwaki, Nagahiro Saijo, Masahiro Fukuoka
Journal: Journal of Thoracic Oncology (2009)

IntroductionRecent pivotal phase III studies in patients with advanced non-small cell lung cancer (NSCLC) consistently showed greater survival benefit of pemetrexed in patients with nonsquamous cell carcinoma histology (nonsquamous histology) compared with those with squamous cell carcinoma histology (squamous histology). To confirm the efficacy differences of pemetrexed by histologic type, we conducted an additional subgroup analysis of data from a Japanese randomized phase II study evaluating the efficacy and safety of pemetrexed 500 mg/m2 (P500) and 1000 mg/m2 (P1000) in patients with advanced NSCLC previously treated with chemotherapy. The efficacy and safety results of original phase II study have already been reported (Ohe et al., Clin Cancer Res 2008;14:4206–4212).MethodsObjective response rates (ORRs), overall survival time, and progression-free survival time were analyzed by subgroup of histology, squamous, and nonsquamous, for the dose groups combined and separately.ResultsA total of 216 patients were evaluable for efficacy. One hundred sixty-eight patients had nonsquamous and 48 had squamous histology. ORRs were 20.8% and 2.1% (p < 0.001); median survival times (MST) were 16.0 and 8.5 months (p < 0.001); and median progression-free survival times (PFS) were 3.1 and 1.6 months (p < 0.001) for nonsquamous and squamous histology, respectively. In patients who were randomized to the P500 group, ORR were 23.5% and 0% (p = 0.0062); MST were 19.4 and 7.9 months (p < 0.001); and PFS were 3.1 and 1.4 months (p < 0.001) for nonsquamous and squamous histology, respectively. In patients who were randomized to the P1000 group, ORR were 18.1% and 4.0% (p = 0.1113); MST were 13.5 months and 8.6 months (p = 0.0971); and PFS were 3.1 and 1.7 months (p = 0.0024) for nonsquamous and squamous histology, respectively. There were no clinically relevant differences in the incidence of toxicities between histology groups.ConclusionsThis study showed the difference of pemetrexed efficacy by histologic type, and this result supports the treatment-by-histology effect observed in the past pivotal phase III studies. Higher dose of pemetrexed resulted in similar outcomes both in patients with nonsquamous histology and squamous histology. Pemetrexed is not as effective as alternative therapies for previously treated squamous histology; however, pemetrexed should be the key agent for the treatment of patients with nonsquamous histology.
Exchange Transfusion in the Newborn-Reply
Authors: Albert Ehrlich
Journal: JAMA (1963)

I agree with Drs. Barnett and Minor that our statistical evidence condemning the use of Group O Rh negative blood for exchange transfusion with Group A and B Rh hemolytic babies is not conclusive. However, common sense analyses are presented of violations of the fundamental findings of Landsteiner and Wiener, revealing the danger of the indiscriminate use of Group O Rh negative blood. Reasonable people do not wait for 100% proof to change from a practice that is at least theoretically dangerous to one that is immunologically safe. Why do I criticize "a successful treatment which has saved hundreds of infants"? We all know that many sick people recover from serious illness in spite of some medical intervention rather than because of such treatment. In exchange transfusions of Rh hemolytic babies, I would like to focus on the 2% mortality per exchange transfusion and show that exchange transfusions of nonspecific
Effect of a Chicken-Based Diet on Renal Function and Lipid Profile in Patients With Type 2 Diabetes
Authors: Jorge L. Gross, Themis Zelmanovitz, Cileide C. Moulin, Vanessa De Mello, Magda Perassolo, Cristiane Leitão, Alice Hoefel, Alexandre Paggi, Mirela J. Azevedo
Journal: Diabetes Care (2002)

OBJECTIVE—To assess the effect of replacing red meat with chicken in the usual diet and the effect of a low-protein diet on glomerular filtration rate (GFR), urinary albumin excretion rate (UAER), and lipid levels in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS—A randomized, crossover, controlled trial was conducted with 28 patients with type 2 diabetes (seven women; mean age 58.1 years): 15 patients were normoalbuminuric (UAER &amp;lt;20 μg/min), and 13 patients were microalbuminuric (UAER 20–200 μg/min). A chicken-based diet (red meat replaced with chicken) and a low-protein diet were compared with the patients’ usual diet. Patients followed each diet for 4 weeks with a 4-week washout period between. GFR (51Cr-EDTA single-injection technique), 24-h UAER (immunoturbidimetry), apolipoprotein B, total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides were measured after each diet. RESULTS—Normoalbuminuric and microalbuminuric patients with diabetes were analyzed separately. In normoalbuminuric patients, GFR after the chicken (101.3 ± 22.9 ml · min−1 · 1.73 m−2) and low-protein diets (93.8 ± 20.5 ml · min−1 · m−2) was lower than after the usual diet (113.4 ± 31.4 ml · min−1 · 1.73 m−2; P &amp;lt; 0.05). In microalbuminuric patients, apolipoprotein B levels were lower after the chicken (113.5 ± 36.0 mg/dl) and low-protein diets (103.5 ± 40.1 mg/dl) than after the usual diet (134.3 ± 30.7 mg/dl; P &amp;lt; 0.05). Only the chicken diet reduced UAER (median 34.3 μg/min) compared with the low-protein (median 52.3 μg/min) and usual (median 63.8 μg/min) diets (P &amp;lt; 0.05). Glycemic control and blood pressure did not change after the diets. CONCLUSIONS—A normoproteic diet with chicken as the only source of meat may represent an alternative strategy for treatment of patients with type 2 diabetes and microalbuminuria.
Deoxyribonucleic acid triplex formation inhibits granulocyte macrophage colony-stimulating factor gene expression and suppresses growth in juvenile myelomonocytic leukemic cells.
Authors: M Kochetkova, P O Iversen, A F Lopez, M F Shannon
Journal: Journal of Clinical Investigation (1997)

Juvenile myelomonocytic leukemia (JMML) is a severe childhood malignancy. The autocrine production of GMCSF is believed to be responsible for the spontaneous proliferation of JMML cells. A nuclear factor-kappaB (NF-kappaB)/Rel binding site within the GM-CSF gene promoter, termed the kappaB element, plays an important role in controlling transcription from the GM-CSF gene. We investigated the effect of an oligonucleotide GM3, directed to form a DNA triple helix across this kappaB element, on growth and GM-CSF production by JMML cells. Treatment of these cells, either unstimulated or induced by TNFalpha, with GM3 led to a significant and specific inhibition of both GM-CSF production and spontaneous colony formation. This constitutes the first report linking specific triplex-mediated inhibition of gene transcription with a functional outcome; i.e., cell growth. We observed the constitutive presence of NF-kappaB/Rel proteins in the nucleus of JMML cells. The constitutive and TNFalpha-induced NF-kappaB/Rel complexes were identical and were composed mainly of p50 and c-Rel proteins. Treatment of the cells with a neutralizing anti-TNFalpha monoclonal antibody completely abrogated constitutive nuclear expression of NF-kappaB/Rel proteins. These results indicate that the aberrant, constitutive GM-CSF gene activation in JMML is maintained by TNFalpha-mediated activation of NF-kappaB/Rel proteins. Our findings identify the molecular basis for the autocrine TNFalpha activation of the GM-CSF gene in JMML and suggest potential novel and specific approaches for the treatment of this aggressive childhood leukemia.
1085 VIRAL HEPATITIS B AND C IN NEWLY DIAGNOSED HIV-1 INDIVIDUALS IN SPAIN – A NATIONAL SURVEY SINCE YEAR 2000
Authors: A. Treviñno, C. Rodriguez, P. Parra, P. Rivas, M.D. Herrero-Mendoza, J. del Romero, V. Soriano, C. de Mendoza
Journal: Journal of Hepatology (2010)
Importance of Gonadal Steroids to Bone Mass in Men with Hyperprolactinemic Hypogonadism
Authors: Susan L. Greenspan
Journal: Annals of Internal Medicine (1989)

Study Objective: To determine the effects of alteration of gonadal steroids on bone mass in men with hyperprolactinemic hypogonadism. Design: Prospective survey of patients for a median period of 33 months. Setting: Neuroendocrine clinical center of a referral-based university medical center. Interventions: Reversal of hyperprolactinemia by bromocriptine therapy, transsphenoidal surgery, or radiation therapy, alone or in combination. Patients: Consecutive sample of 20 male patients with prolactin-secreting pituitary tumors. Measurements and Main Results: In patients who had a reversal of hyperprolactinemia and a restoration of gonadal function, a significant increase in bone density of the radial shaft was noted (mean ± SE, 0.77 ± 0.03 to 0.84 ± 0.03 g/ cm2; P ≤ 0.05). These patients also had a minimal change in the density of vertebral bone (109 ± 9 to 115 ± 10 mg of potassium phosphate, dibasic/cm3). Patients who remained hypogonadal despite the reversal of hyperprolactinemia had no change in radial (0.76 ± 0.03 to 0.76 ± 0.04 g/cm2) or vertebral bone density (105 ± 10 to 103 ± 9 mg of potassium phosphate, dibasic/cm3). There was a positive correlation between the change in testosterone level and the change in radial (r = 0.67, P ≤ 0.003) or vertebral bone density (r = 0.70, P ≤ 0.003). Conclusions: The reversal of hypogonadism, independent of the prolactin concentration, is associated with an improvement in bone mass. Our findings emphasize the importance of gonadal steroids in maintaining skeletal integrity in men.
Fox Postnasal Balloon For Control of Bleeding
Authors: Bernard R. Levinthal
Journal: JAMA (1971)

<h3>To the Editor.—</h3> Those of your readers who are accustomed to the use of a Fox postnasal balloon for the control of bleeding in that area should be made aware of a potential hazard associated with its use. Recently, after inserting a Fox postnasal balloon for the control of adenoidectomy bleeding, after an adenotonsillectomy under general anesthesia, the balloon was discovered to have come apart, following the return of the patient to the recovery room. As those who use it know, this device consists of a soft latex balloon attached to a firm rubber catheter by a silk ligature. In this particular case, the catheter was found lying on the bed without the balloon. The patient subsequently expectorated the balloon from the nasopharynx, with no further problems. Needless to say, had the patient been still more under the effects of the anesthesia, she could have aspirated the balloon, with potential
Near‐Infrared Fluorescent Silica‐Coated Gold Nanoparticle Clusters for X‐Ray Computed Tomography/Optical Dual Modal Imaging of the Lymphatic System
Authors: Koichiro Hayashi, Michihiro Nakamura, Kazunori Ishimura
Journal: Advanced Healthcare Materials (2012)

Lymph nodes (LNs) are often removed to prevent the spread of cancer because they are frequently the first site of metastases. However, the enucleation of LNs requires difficult operative techniques and lymphedema can result as a complication. Although lymphedema can be cured by anastomosis of a lymph vessel (LV) to a vein, the operative procedure is extremely difficult because LNs and LVs are too small and indistinct to be identified. Therefore, visualization of LNs and LVs is important. The combination of X-ray computed tomography (CT) and fluorescence imaging, CT/fluorescence dual modal imaging, enables the visualization of LNs and LVs before and during surgery. To accomplish this, near-infrared fluorescent silica-coated gold nanoparticle clusters (Au@SiO₂) with a high X-ray absorption coefficient are synthesized. Both fluorescence imaging and CT show that the Au@SiO₂ nanoparticles gradually accumulate in LNs through LVs. CT determines the location and size of the LNs and LVs without dissection, and fluorescence imaging facilitates their identification. The Au@SiO₂ nanoparticles have neither hepatotoxicity nor nephrotoxicity. The results demonstrate that CT/fluorescence dual modal imaging using Au@SiO₂ nanoparticles provides anatomical information, including the location and size of LNs and LVs for determining a surgery plan, and provides intraoperative visualization of LNs and LVs to facilitate the operation.