tbuckley/cabot-search huggingface dataset:
Renal Status Among Patients Using Metformin in a Primary Care Setting
Authors: Laurence Kennedy, William H. Herman
Journal: Diabetes Care (2005)

Metformin use has been associated with lactic acidosis, a rare but potentially lethal condition characterized by elevated blood lactate levels (>5 mmol/l), an increased lactate-to-pyruvate ratio, and an increased anion gap (1). Most cases of metformin-associated lactic acidosis occur in patients with preexisting conditions (e.g., renal insufficiency, hepatic impairment, or heart failure) (2). When used as labeled, metformin may not increase the risk of lactic acidosis beyond what already exists with such conditions (3–5). However, despite evidence suggesting that the risk of lactic acidosis may be reduced if metformin is avoided in patients with renal impairment, and despite the ready availability of serum creatinine tests to assess renal function, inappropriate prescribing of metformin is a concern (2,3,6–9).

The randomized, open-label Glycemic Optimization with Algorithms and Labs At Po1nt of Care (GOAL A1C) study was designed to evaluate the impact of point-of-care versus laboratory testing of glycosylated hemoglobin (A1C) and monitored versus standard titration of insulin glargine on glycemic control in patients with type 2 diabetes inadequately controlled on oral agents. This study also provided an opportunity to assess appropriateness of metformin therapy based on serum creatinine levels at enrollment in a large, predominantly primary care population. This assessment forms the basis of …
Mandibular advancement devices for the control of snoring
Authors: None Stradling, TW Negus, D Smith, B Langford
Journal: European Respiratory Journal (1998)

Patients presenting with the complaint of antisocial snoring have very few options available to them of proven efficiency. Mandibular advancement devices worn intra-orally at night, have recently been shown in controlled trials to help mild to moderate obstructive sleep apnoea. However, there are no properly controlled studies with objective measurements on the use of such appliances for the management of antisocial snoring. Fifteen patients, already established on mandibular advancement devices for the control of snoring, were asked to participate in this study. They were studied over two nights, using a portable sleep monitoring device at home, both with and without their mandibular advancement devices in place (in randomized order). Snoring was measured using a surface throat microphone. In addition oxygen saturation and indirect beat to beat blood pressure were measured. The latter (using pulse transit time) provided an index of autonomic "arousals" and a measure of inspiratory effort. In nearly all of these highly selected patients the mandibular advancement devices reduced significantly the amount of snoring from a median of 193 to 20 snores x h(-1) (p&lt;0.0001). In addition there was a reduction in respiratory effort, implying enlargement of the upper airway whilst wearing the appliance. These patients only represent those who were able to tolerate the appliance. With such clear evidence of their potential efficacy, and no suggestion from other studies of any harm, it would seem reasonable to introduce this approach into the management of antisocial snoring.
Dose-dependent Effects of Inhaled Mometasone Furoate on Airway Function and Inflammation After Allergen Inhalation Challenge
Authors: MARK D. INMAN, RICHARD M. WATSON, TACY RERECICH, GAIL M. GAUVREAU, BARRY N. LUTSKY, PAUL STRYSZAK, PAUL M. O'BYRNE
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Comparisons of the potency of different inhaled corticosteroids, delivery devices, and treatment regimens in the management of asthma can only be made when outcome measurements display a dose-dependent effect. These outcomes have been difficult to identify. In this study, we compared in a randomized, double-blind, crossover design, the effects of 6 d treatment with placebo and three doses (50, 100, and 400 μ g, twice daily) of mometasone furoate delivered by dry powder inhaler (MF-DPI) on responses after allergen inhalation challenge. Twelve mild asthmatic subjects with dual responses after allergen inhalation were studied. Outcome measurements included early and late asthmatic responses, the change in methacholine airway responsiveness 24 h after challenge, and sputum eosinophilia measured 7 and 24 h after challenge. All three doses of MF-DPI demonstrated similar attenuation of early responses and allergen-induced airway hyperresponsiveness relative to placebo (p < 0.05). The late maximal %fall in FEV1 after placebo treatment was 23.5% and was significantly reduced in a dose-dependent manner to 12.3%, 11.0%, and 5.9% for the 50-, 100-, and 400- μ g twice-daily treatments (p = 0.007). The allergen-induced increase in sputum eosinophilia ( × 104 cells / ml) 24 h after challenge during placebo treatment was 60.2 and was significantly reduced to 24.0, 15.3, and 6.2 for the 50-, 100-, and 400- μ g twice-daily treatments. MF-DPI is effective at attenuating allergen-induced early and late responses, airway hyperresponsiveness, and sputum eosinophilia, and dose–response effects exist for the attenuation of the late response.Keywords: asthma; allergen-challenge; inflammation; corticosteroid
254. Vaccination of Recurrent Glioma Patients with Tumour Lysate-Pulsed Dendritic Cells Elicits Immune Responses: Results of a Clinical Phase I/II Trial
Journal: Molecular Therapy (2004)

In this Phase I/II trial, the patient's peripheral blood dendritic cells were pulsed with an autologous tumour lysate of the glioma. Fourteen patients with glioblastoma and 4 patients with anaplastic glioma, ranging in age from 20 to 73 years, participated in this study. The mean numbers of vaccinations of tumour lysate-pulsed dendritic cells were 4.8 times intradermally close to a cervical lymph node, and 4.2 times intratumourally via an Ommaya reservoir. The percentage of CD56-positive cells in the peripheral blood lymphocytes increased after immunization. There were 1 partial response, 2 minor responses and 7 no change cases evaluated by radiological findings. Dendritic cell vaccination elicited T-cell-mediated antitumour activity, as evaluated by ELISPOT assay after vaccination in 2 of 5 tested patients. Three patients showed DTH reactivity to the autologous tumour lysate, two of these had a minor clinical response, and two had an increased ELISPOT result. Intratumoural CD4 and CD8 T-cell infiltration was detected in two patients who underwent re-operation after vaccination. This study demonstrated the safety and antitumour effects of autologous tumour lysate-pulsed dendritic cell therapy for patients with malignant glioma.
N-methyl-N'-nitro-N-nitrosoguanidine-induced senescence-like growth arrest in colon cancer cells is associated with loss of adenomatous polyposis coli protein, microtubule organization, and telomeric DNA.
Authors: Aruna S Jaiswal, Asha S Multani, Sen Pathak, Satya Narayan
Journal: Molecular Cancer (2004)

Cellular senescence is a state in which mammalian cells enter into an irreversible growth arrest and altered biological functions. The senescence response in mammalian cells can be elicited by DNA-damaging agents. In the present study we report that the DNA-damaging agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) is able to induce senescence in the HCT-116 colon cancer cell line. Cells treated with lower concentrations of MNNG (0–25 microM) for 50 h showed a dose-dependent increase in G2/M phase arrest and apoptosis; however, cells treated with higher concentrations of MNNG (50–100 microM) showed a senescence-like G0/G1 phase arrest which was confirmed by increased expression of β-galactosidase, a senescence induced marker. The G2/M phase arrest and apoptosis were found to be associated with increased levels of p53 protein, but the senescence-like G0/G1 phase arrest was dissociated with p53 protein levels, since the p53 protein levels decreased in senescence-like arrested cells. We further, determined whether the decreased level of p53 was a transcriptional or a translational phenomenon. The results revealed that the decreased level of p53 protein in senescence-like arrested cells was a transcriptional phenomenon since p53 mRNA levels simultaneously decreased after treatment with higher concentrations of MNNG. We also examined the effect of MNNG treatment on other cell cycle-related proteins such as p21, p27, cyclin B1, Cdc2, c-Myc and max. The expression levels of these proteins were increased in cells treated with lower concentrations of MNNG, which supported the G2/M phase arrest. However, cells treated with higher concentrations of MNNG showed decreased levels of these proteins, and hence, may not play a role in cell cycle arrest. We then examined a possible association of the expression of APC protein and telomeric DNA signals with cellular senescence in MNNG-treated cells. We found that protein and mRNA levels of APC were drastically reduced in cells treated with higher concentrations of MNNG. The loss of APC expression might lead to chromosomal instability as well as microtubular disorganization through its dissociation with tubulin. In fact, the protein level of α-tubulin was also drastically decreased in senescence-like arrested cells treated with higher concentrations of MNNG. The levels of telomeric DNA also decreased in cells treated with higher concentrations of MNNG. These results suggest that in response to DNA alkylation damage the senescence-like arrest of HCT-116 cells was associated with decreased levels of APC protein, microtubular organization, and telomeric DNA.
Glycemic Status and Brain Injury in Older Individuals
Authors: Jane S. Saczynski, Sigurdur Siggurdsson, Palmi V. Jonsson, Gudny Eiriksdottir, Elin Olafsdottir, Olafur Kjartansson, Tamara B. Harris, Mark A. van Buchem, Vilmundur Gudnason, Lenore J. Launer
Journal: Diabetes Care (2009)

OBJECTIVE To examine the association of glycemic status to magnetic resonance imaging indicators of brain pathological changes. RESEARCH DESIGN AND METHODS This was a cross-sectional, population-based study of 4,415 men and women without dementia (mean age 76 years) participating in the Age Gene/Environment Susceptibility–Reykjavik Study. Glycemic status groups included the following: type 2 diabetes (self-report of diabetes, use of diabetes medications, or fasting blood glucose ≥7.0 mmol/l [11.1%]); impaired fasting glucose (IFG) (fasting blood glucose 5.6–6.9 mmol/l [36.2%]); and normoglycemic (52.7%). Outcomes were total brain volume, white and gray matter volume, white matter lesion (WML) volume, and presence of cerebral infarcts. RESULTS After adjustment for demographic and cardiovascular risk factors, participants with type 2 diabetes had significantly lower total brain volume (72.2 vs. 71.5%; P &amp;lt; 0.001) and lower gray and white matter volumes (45.1 vs. 44.9%, P &amp;lt; 0.01 and 25.7 vs. 25.3%, P &amp;lt; 0.001, respectively) and were more likely to have single (odds ratio 1.45 [95% CI 1.14–1.85]) or multiple (2.27 [1.60–3.23]) cerebral infarcts compared with normoglycemic participants. Longer duration of type 2 diabetes was associated with lower total brain volume and gray and white matter volume, higher WML volume (all Ptrend &amp;lt; 0.05), and a greater likelihood of single and multiple cerebral infarcts (all Ptrend &amp;lt; 0.01). CONCLUSIONS Type 2 diabetic participants have more pronounced brain atrophy and are more likely to have cerebral infarcts. Duration of type 2 diabetes is associated with brain changes, suggesting that type 2 diabetes has a cumulative effect on the brain.
Anti–Cytotoxic T-Lymphocyte Antigen-4 Antibody: The First in an Emerging Class of Immunomodulatory Antibodies for Cancer Treatment
Authors: Lawrence Fong, Eric J. Small
Journal: Journal of Clinical Oncology (2008)

To evaluate the emerging role of immunomodulatory antibodies in cancer treatment. Antibodies (ipilimumab and tremelimumab) targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4), an inhibitory molecule on T cells, represent the vanguard of these new drugs.We performed a systematic review of the clinical studies examining the clinical activity of anti-CTLA-4 antibodies. We also review the potential mechanisms and toxicities associated with these treatments.Clinical activity with anti-CTLA-4 monoclonal antibodies (mAbs) has paved the way for additional T-cell immunomodulatory monoclonal antibody (mAb) approaches for the treatment of cancer to be investigated. Because anti-CTLA-4 mAbs target the immune system and not the tumor, they may provide significant potential advantages over traditional antitumor mAbs, chemotherapies, and immunotherapies (ie, vaccines and cytokines). Other antibodies, such as CD137 agonists, CD40 agonists, and PD-1 antagonists, are currently in various stages of preclinical and clinical development.Available clinical data suggest that anti-CTLA-4 mAbs are very different from traditional mAbs, chemotherapies, and immunotherapies in terms of patterns of response, duration of response, and adverse event profile. Ongoing clinical studies aim to establish the efficacy and safety of anti-CTLA-4 mAbs as monotherapy or in combination with other drugs for the treatment of metastatic melanoma and a variety of other cancer types.
Obstruction of the fetal urinary tract.
Authors: C A Peters
Journal: Journal of the American Society of Nephrology (1997)

Understanding the mechanisms of fetal obstructive uropathy will be essential for the specific management of the wide clinical spectrum of congenital obstructive conditions, including selecting observational therapy for mild cases and attempting to maximize renal function in severe cases. Recognition of the unique aspects of fetal renal obstruction is essential to formulate a useful research program, as the lessons of postnatal acquired obstruction are not directly transferable to congenital obstruction. Experimental studies of renal obstruction have demonstrated alterations in the developmental regulation of growth and differentiation in the fetal kidney. Depending on the gestational timing and severity of obstruction, growth may be impaired or accelerated. Similarly, patterns of altered differentiation may indicate immaturity or accelerated maturation, as well as aberrant differentiation. Concomitant with altered development, there is evidence that normal renal regulatory mechanisms, including the renin-angiotensin system and renal hemodynamics, may be affected by obstruction, possibly as compensatory responses. The mechanisms of these various alterations remain to be defined, but are likely to involve combinations of biomechanical signal transduction, growth factor expression, and responses of specific renal autoregulatory mechanisms. Fetal renal obstruction remains incompletely defined. The body of experimental evidence indicates that investigation of mechanisms regulating growth and differentiation is likely to yield important understanding of fetal renal obstruction to permit more accurate prognosis and management. Viewing fetal renal obstruction as a disorder of kidney development, with disordered growth and differentiation, suggests a definition of obstruction as a condition, that--if uncorrected--will lead to impairment in the ultimate functional potential of the kidney. Intervention should aim to maximize functional potential rather than to simply maintain the status quo.
Randomized Trial of Antioxidant Vitamins to Prevent Acute Adverse Effects of Radiation Therapy in Head and Neck Cancer Patients
Authors: Isabelle Bairati, François Meyer, Michel Gélinas, André Fortin, Abdenour Nabid, François Brochet, Jean-Philippe Mercier, Bernard Têtu, François Harel, Belkacem Abdous, Éric Vigneault, Sylvie Vass, Pierre del Vecchio, Jean Roy
Journal: Journal of Clinical Oncology (2005)

Many cancer patients take antioxidant vitamin supplements with the hope of improving the outcome of conventional therapies and of reducing the adverse effects of these treatments. A randomized trial was conducted to determine whether supplementation with antioxidant vitamins could reduce the occurrence and severity of acute adverse effects of radiation therapy and improve quality of life without compromising treatment efficacy.We conducted a randomized, double-blind, placebo-controlled trial among 540 head and neck cancer patients treated with radiation therapy. Patients were randomly assigned into two arms. The supplementation with alpha-tocopherol (400 IU/d) and beta-carotene (30 mg/d) or placebos was administered during radiation therapy and for 3 years thereafter. During the course of the trial, supplementation with beta-carotene was discontinued because of ethical concerns.Patients randomly assigned in the supplement arm tended to have less severe acute adverse effects during radiation therapy (odds ratio [OR], 0.72; 95% CI, 0.52 to 1.02). The reduction was statistically significant when the supplementation combined alpha-tocopherol and beta-carotene for adverse effects to the larynx (OR, 0.38; 95% CI, 0.21 to 0.71) and overall at any site (OR, 0.38; 95% CI, 0.20 to 0.74). Quality of life was not improved by the supplementation. The rate of local recurrence of the head and neck tumor tended to be higher in the supplement arm of the trial (hazard ratio, 1.37; 95% CI, 0.93 to 2.02).Supplementation with high doses of alpha-tocopherol and beta-carotene during radiation therapy could reduce the severity of treatment adverse effects. However, this trial suggests that use of high doses of antioxidants as adjuvant therapy might compromise radiation treatment efficacy.
Increased Levels of Nitrate and Surfactant Protein A Nitration in the Pulmonary Edema Fluid of Patients with Acute Lung Injury
Authors: SHA ZHU, LORRAINE B. WARE, THOMAS GEISER, MICHAEL A. MATTHAY, SADIS MATALON
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Levels of nitrite (NO2 −) and nitrate (NO3 −) were measured in pulmonary edema fluid and plasma from 34 patients with early acute lung injury (ALI) and 20 patients with hydrostatic pulmonary edema. Pulmonary edema fluid from patients with ALI had significantly higher levels of NO2 − + NO3 − compared with pulmonary edema fluid from patients with hydrostatic pulmonary edema (108 ± 13 μ M versus 66 ± 9 μ M; means ± SEM; p < 0.05). In addition, patients with shock had higher plasma NO2 − + NO3 − levels than those without shock (79 ± 11 μ M versus 53 ± 12 μ M, p < 0.05). Acidemia and increased anion gap, markers of systemic hypoperfusion, were also associated with twofold higher plasma NO2 − + NO3 − levels (p < 0.01). Increased levels of NO2 − + NO3 − in edema fluid samples were associated with slower rates of alveolar fluid clearance. Nitrated pulmonary surfactant protein A (SP-A) was also detected in the edema fluid of patients with ALI after immunoprecipitation with a specific antibody against this protein. Previously, we have shown that nitration of SP-A impairs its host– defense properties. In aggregate, the results of this study indicate that reactive oxygen–nitrogen species may play a role in the pathogenesis of human ALI.
Aetiology of scrapie in certain circumstances is not evidence against another aetiology in different circumstances
Authors: R M Ridley, H F Baker
Journal: BMJ (1996)

Magnetic resonance imaging may have a role in diagnosing Creutzfeldt-Jakob disease EDITOR,-Creutzfeldt-Jakob disease' is still rarely diagnosed in Britain, and neuropathological examination is required to confirm the diagnosis.Research in the United States, however, has shown the presence of bilaterally symmetric hyperintense abnormalities in the basal ganglia in T2 weighted magnetic resonance images in patients with pathologically proved Creutzfeldt-Jakob disease.2This abnormality on magnetic resonance imaging was first reported in 1988.3A colleague and I have reported Creutzfeldt-Jakob disease, with signal abnormalities in the basal ganglia on magnetic resonance imaging, in a 58 year old man with no occupational exposure to animals who presented with progressive dementia.4The prevalence of hyperintense abnormalities in the basal ganglia in T2 weighted images in patients with Creutzfeldt-Jakob disease has not been studied and remains unknown.Such hyperintense abnormalities in the basal ganglia can be seen in several disorders, but a combination of clinical features, laboratory findings, and imaging characteristics can be used to distinguish the other conditions from Creutzfeldt-Jakob disease.Although the absence of bilateral symmetric hyperintense lesions in the basal ganglia does not exclude Creutzfeldt-Jakob disease, it is reasonable to assume that their presence in patients with rapidly progressive dementia is a specific sign of the disease.It would be useful to know of other documented cases in which magnetic resonance imaging was carried out before death.Surely it would be worth while pursuing further research in this field and collating data from several centres with an interest in Creutzfeldt-Jakob disease to evaluate the role of magnetic resonance imaging in this condition.
Obsessive-Compulsive Disorder in Adolescent Schizophrenia Patients
Authors: Allon Nechmad, Gideon Ratzoni, Michael Poyurovsky, Sorin Meged, Gideon Avidan, Camil Fuchs, Yuval Bloch, Ronit Weizman
Journal: American Journal of Psychiatry (2003)

The co-occurrence of obsessive-compulsive disorder (OCD) in adult patients with schizophrenia has been increasingly recognized. However, the rate of OCD comorbidity in adolescent schizophrenia patients has yet to be systematically evaluated.The rate of DSM-IV OCD was evaluated in 50 adolescent inpatients with schizophrenia or schizoaffective disorder. The severity of schizophrenia and OCD symptoms was assessed with the Scale for the Assessment of Positive Symptoms, Scale for the Assessment of Negative Symptoms (SANS), and Yale-Brown Obsessive Compulsive Scale.Thirteen schizophrenia patients (26.0%) also met the DSM-IV criteria for OCD. This subgroup scored significantly higher on the SANS subscale for affective flattening or blunting. The total SANS score positively correlated with the total Yale-Brown Obsessive Compulsive Scale score.A substantial proportion of adolescent schizophrenia inpatients have concomitant OCD. A prospective study is needed to evaluate the clinical course, response to treatment, and prognosis for this complex disorder.
Progenitor of all trades
Authors: Heather L. Van Epps
Journal: The Journal of Experimental Medicine (2005)

Despite years of research, the identity of the bone marrow progenitor cells that seed the thymus, as well as the place where they ultimately commit to being T cells, have remained elusive. On page 21, Benz and Bleul identify the first multipotent progenitor cell in the adult thymus. The new data suggest that, for at least some progenitor cells, commitment to a T cell fate occurs after arrival in the thymus.

Populations of thymic precursor cells have been shown to generate multiple cell lineages, but it remains a matter of debate whether single precursor cells can give rise to all the possible thymic cell lineages—T cells, B cells, and dendritic cells (DCs).

Benz and Bleul now show that these cell types can indeed arise from a single precursor cell. By fusing EGFP with a marker of T cell development sites (CCR9), they pinpointed a small population of cells in the bone marrow that was able to populate the thymus.

Single-cell sorting of these precursor cells from the thymus revealed that a single cell could generate T cells, B cells and DCs, suggesting that these progenitor cells commit to a T cell fate in the thymus. Thymic cells with the same surface markers but lower levels of EGFP—presumably representing a slightly more mature population of cells (with decaying EGFP)—were no longer able to generate B cells, suggesting that the EGFP+ population marks the branching point of the T and B cell lineages.