tbuckley/cabot-search huggingface dataset:
Novel Assay of Metformin Levels in Patients With Type 2 Diabetes and Varying Levels of Renal Function
Authors: Anders Frid, Gunnar N. Sterner, Magnus Löndahl, Clara Wiklander, Anne Cato, Ellen Vinge, Anders Andersson
Journal: Diabetes Care (2010)

OBJECTIVE To study trough levels of metformin in serum and its intra-individual variation in patients using a newly developed assay. RESEARCH DESIGN AND METHODS Trough serum levels of metformin were measured once using liquid chromatography–tandem mass spectrometry (LCMSMS) in 137 type 2 diabetic patients with varying renal function (99 men) and followed repeatedly during 2 months in 20 patients (16 men) with estimated glomerular filtration rate (eGFR) &amp;lt;60 ml/min/1.73 m2 body surface. RESULTS Patients with eGFR &amp;gt;60, 30–60, and &amp;lt;30 ml/min/1.73 m2 had median trough metformin concentrations of 4.5 μmol/l (range 0.1–20.7, n = 107), 7.71 μmol/l (0.12–15.15, n = 21), and 8.88 μmol/l (5.99–18.60, n = 9), respectively. The median intra-individual overall coefficient of variation was 29.4% (range 9.8–74.2). CONCLUSIONS Determination of serum metformin with the LCMSMS technique is useful in patients on metformin treatment. Few patients had values &amp;gt;20 μmol/l. Metformin measurement is less suitable for dose titration.
Levofloxacin-based and clarithromycin-based triple therapies as first-line and second-line treatments for Helicobacter pylori infection: a randomised comparative trial with crossover design
Authors: J. M. Liou, J. T. Lin, C. Y. Chang, M. J. Chen, T. Y. Cheng, Y. C. Lee, C. C. Chen, W. H. Sheng, H. P. Wang, M. S. Wu
Journal: Gut (2010)

<h3>Background</h3> The efficacy of a levofloxacin-based regimen as the first-line treatment and a clarithromycin-based regimen as the second-line treatment for <i>Helicobacter pylori</i> infection remains unknown. The aim of this study was to assess the eradication rates of these two regimens using different administration sequences. <h3>Methods</h3> Eligible patients were randomised to receive LAL: levofloxacin (750 mg once a day), amoxicillin (1000 mg twice a day) and lansoprazole (30 mg twice a day) for 7 days, or CAL: clarithromycin (500 mg twice a day), amoxicillin (1000 mg twice a day) and lansoprazole (30 mg twice a day) for 7 days. Patients with positive [<sup>13</sup>C]urea breath test after treatment were retreated with the rescue regimen in a crossover manner for 10 days. <h3>Result</h3> When used as first-line treatment (n=432), the eradication rates of LAL (n=217) and CAL (n=215) were 74.2 and 83.7% (p=0.015) in the intent-to-treat (ITT) analysis, and 80.1 and 87.4% (p=0.046) in the per-protocol (PP) analysis, respectively. When used as second-line treatment, the eradication rates of LAL (n=26) and CAL (n=40) were 76.9 and 60% (p=0.154) in the ITT analysis, and 80 and 61.5% (p=0.120) in the PP analysis, respectively. The overall eradication rates of CAL followed by LAL were better than the reverse sequence in both the ITT analysis (93% vs 85.3%, p=0.01) and the PP analysis (97.6% vs 92.5%, p=0.019). The eradication rate was significantly lower in the presence of levofloxacin resistance in the LAL group (50% vs 84.4%, p=0.018) and clarithromycin resistance in the CAL group (44.4% vs 90.7%, p=0.002). <h3>Conclusion</h3> CAL achieved a higher eradication rate than LAL as the first-line treatment, but not as the second-line treatment. The strategy of using CAL as the initial treatment and LAL as the rescue regimen achieved higher eradication rates than the reverse sequence. <b>Clinical trial number</b> NCT00816140.
Kaposi Sarcoma Incidence and Survival Among HIV-Infected Homosexual Men After HIV Seroconversion
Authors: S. Lodi, M. Guiguet, D. Costagliola, M. Fisher, A. de Luca, K. Porter
Journal: JNCI Journal of the National Cancer Institute (2010)

Despite the success of combination antiretroviral therapy (cART) in reducing the incidence of Kaposi sarcoma, HIV-infected individuals who have responded to treatment continue to be diagnosed with Kaposi sarcoma. We examine factors associated with the incidence of Kaposi sarcoma among cART-treated HIV-infected homosexual men and changes in their survival after its diagnosis over calendar time. Data were from HIV-infected homosexual men with well-estimated dates of HIV seroconversion (ie, change in status from being HIV negative to having HIV antibodies detected). Incidence of Kaposi sarcoma was calculated. We used Kaplan–Meier methods to determine survival after Kaposi sarcoma diagnosis in three calendar periods: before 1996, 1996–2000, and 2001–2006. Poisson models were used to examine the effect of risk factors such as current and nadir CD4 cell count (ie, the lowest CD4 cell count ever recorded for a person), duration of infection, and age at diagnosis for Kaposi sarcoma incidence in cART-treated men. All statistical tests were two-sided. Among the 9473 men, 555 were diagnosed with Kaposi sarcoma in the period 1986–2006, of whom 319 died. The percentage surviving 24 months after Kaposi sarcoma diagnosis rose statistically significantly during the study period from 35% (95% confidence interval [CI] = 29% to 42%) before 1996 to 84% (95% CI = 76% to 90%) in 1996–2000 and to 81% (95% CI = 70% to 88%) in 2001–2006 ( P < .001). Seventy men were diagnosed with Kaposi sarcoma after starting cART. Current (ie, within 6 months) CD4 cell count was associated with incidence of Kaposi sarcoma among cART-treated men (rate ratios [RRs] = 18.91, 95% CI = 8.50 to 42.09, for CD4 level category <200 cells per cubic millimeter; RR = 3.55, 95% CI = 1.40 to 9.00, for 200–349 cells per cubic millimeter; and RR = 4.11, 95% CI = 1.74 to 9.70, for 350–499 cells per cubic millimeter; all compared with ≥500 cells per cubic millimeter). After adjustment for current CD4 cell count, HIV infection duration, age, or nadir CD4 cell count was not associated with Kaposi sarcoma incidence. Among cART-treated HIV-infected homosexual men, current CD4 cell count was the factor most strongly associated with the incidence of Kaposi sarcoma. Survival estimates after Kaposi sarcoma diagnosis have improved over time.
What's in a Label? Radioimmunotherapy for Metastatic Prostate Cancer
Authors: Charles B. Simone, Stephen M. Hahn
Journal: Clinical Cancer Research (2013)

Abstract Prostate cancer has a highly tumor-restricted prostate-specific membrane antigen (PSMA) and may be the ideal solid-organ malignancy for treatment with radioimmunotherapy. Encouraging results using lutetium-177–labeled anti-PSMA monoclonal antibody J591 from a phase II study by Tawaga and colleagues support the continued clinical and preclinical development of radioimmunotherapy for solid tumors. Clin Cancer Res; 19(18); 4908–10. ©2013 AACR.
TOTAL MEDICAL TREATMENT: REPORT OF A FIVE-YEAR STUDY
Authors: JOHN MEYER, MARY BUSWELL
Journal: American Journal of Psychiatry (1964)

This is a report of a 5-year research investigation and trial, seeking to determine the size and shape of adequate, effective treatment for sick persons. This treatment has been entitled Total Medical Treatment. The treatment has been discussed under three headings: the Total Appraisal, the Total Plan, the Total Effort. An illustrative case is described. Twelve basic principles are presented. An impression is given of the effectiveness of this treatment.
Duplication and Concerted Evolution of the Mitochondrial Control Region in the Parrot Genus Amazona
Authors: Jessica R. Eberhard, Timothy F. Wright, Eldredge Bermingham
Journal: Molecular Biology and Evolution (2001)

We report a duplication and rearrangement of the mitochondrial genome involving the control region of parrots in the genus Amazona. This rearrangement results in a gene order of cytochrome b/tRNA(Thr)/pND6/pGlu/CR1/tRNA(Pro)/NADH dehydrogenase 6/tRNA(Glu)/CR2/tRNA(Phe)/12s rRNA, where CR1 and CR2 refer to duplicate control regions, and pND6 and pGlu indicate presumed pseudogenes. In contrast to previous reports of duplications involving the control regions of birds, neither copy of the parrot control region shows any indications of degeneration. Rather, both copies contain many of the conserved sequence features typically found in avian control regions, including the goose hairpin, TASs, the F, C, and D boxes, conserved sequence box 1 (CSB1), and an apparent homolog to the mammalian CSB3. We conducted a phylogenetic analysis of homologous portions of the duplicate control regions from 21 individuals representing four species of Amazona (A. ochrocephala, A. autumnalis, A. farinosa, and A. amazonica) and Pionus chalcopterus. This analysis revealed that an individual's two control region copies (i.e., the paralogous copies) were typically more closely related to one another than to corresponding segments of other individuals (i.e., the orthologous copies). The average sequence divergence of the paralogous control region copies within an individual was 1.4%, versus a mean value of 4.1% between control region orthologs representing nearest phylogenetic neighbors. No differences were found between the paralogous copies in either the rate or the pattern in which the two copies accumulated base pair changes. This pattern suggests concerted evolution of the two control regions, perhaps through occasional gene conversion events. We estimated that gene conversion events occurred on average every 34,670 +/- 18,400 years based on pairwise distances between the paralogous control region sequences of each individual. Our results add to the growing body of work indicating that under some circumstances duplicated mitochondrial control regions are retained through evolutionary time rather than degenerating and being lost, presumably due to selection for a small mitochondrial genome.
Stroke Risk and Tamoxifen Therapy for Breast Cancer
Authors: A. M. Geiger, G. M. Fischberg, W. Chen, L. Bernstein
Journal: JNCI Journal of the National Cancer Institute (2004)

Background: Tamoxifen, which is used widely to treat, and increasingly to prevent, breast cancer, has been associated with increased risk of stroke. We assessed the impact of tamoxifen treatment for breast cancer on the risk of stroke, considering dose, duration, and recency of use of tamoxifen and known stroke risk factors. Methods: We conducted a nested case–control study of stroke after breast cancer among female Los Angeles County residents enrolled in a large health maintenance organization when diagnosed with breast cancer between January 1, 1980, and July 1, 2000. We obtained information on breast cancer treatment and stroke risk factors through medical record review and telephone interviews. The association (odds ratio [OR] and 95% confidence interval [CI]) between tamoxifen and stroke risk was determined by using a conditional logistic regression model, adjusting for menopausal status and history of hypertension and diabetes. All statistical tests were two-sided. Results: Of 11 045 women with breast cancer, 179 met stroke eligibility criteria and were individually matched to two stroke-free control subjects with breast cancer on age and year of breast cancer diagnosis. The mean age at breast cancer diagnosis was 66.6 years (standard deviation [SD] = 12.3 years), and the mean at-risk period (i.e., the time between breast cancer diagnosis and first stroke or comparable time period for control subjects) was 5.7 years (SD = 4.5 years). Tamoxifen use was not associated with risk of stroke, either overall (OR = 1.0, 95% CI = 0.6 to 1.6) or in subgroups defined by duration, dose, or recency of use. Chemotherapy, but not a specific chemotherapy regimen, was associated with an increased risk of stroke, regardless of tamoxifen use (no tamoxifen use, OR = 2.8, 95% CI = 1.3 to 6.3; tamoxifen use OR = 2.2, 95% CI = 1.2 to 4.1). Conclusions: Tamoxifen use is not associated with increased stroke risk. Further exploration of possible increased stroke risk following chemotherapy treatment for breast cancer is needed.
Local delivery of r-hirudin by a double-balloon perfusion catheter prevents mural thrombosis and minimizes platelet deposition after angioplasty.
Authors: B J Meyer, A Fernández-Ortiz, A Mailhac, E Falk, L Badimon, A D Michael, J H Chesebro, V Fuster, J J Badimon
Journal: Circulation (1994)

BACKGROUND The major morbidity of percutaneous transluminal coronary angioplasty is acute thrombosis and restenosis of the dilated lesion. Platelet-thrombus deposition occurs within minutes after injury, is primarily mediated by thrombin, causes acute occlusion, and contributes to late restenosis. Experimentally, specific thrombin inhibitors have prevented mural thrombosis. However, local therapy may be more effective than systemic treatment. We tested the hypothesis that high local concentrations of an antithrombin drug at the site of arterial injury following balloon angioplasty inhibit platelet thrombus formation equally or better than conventional systemic treatment and at lower systemic anticoagulant levels. METHODS AND RESULTS Balloon angioplasty of the carotid arteries of 29 pigs was performed using systemic intravenous treatment with heparin (100 U/kg, groups I and II), suboptimal r-hirudin (0.3 mg/kg, group III), and higher-dose r-hirudin (0.7 mg/kg, group IV), which is the lowest dose that completely inhibited arterial thrombosis in the pig. Immediately after balloon angioplasty of the first carotid, additional local therapy with placebo (group I) or r-hirudin (groups II, III, and IV; 0.3 mg/kg in 1 mL) was administered with distal perfusion through a new percutaneous double-balloon catheter. After 1 hour of local drug delivery, angioplasty of the contralateral carotid was performed. Reflow for 1 hour was permitted to both carotids to compare the short-term effect of local plus systemic treatment with systemic treatment on quantitative 111In-labeled platelet deposition and macroscopic mural thrombus formation on deeply injured carotid segments. Local drug delivery of placebo compared with systemic heparin treatment resulted in no change of platelet deposition (x 10(6)/cm2, mean +/- SEM) in controls (group I, 91.0 +/- 23.5 versus 80.8 +/- 19.4), but local delivery of r-hirudin resulted in a significant reduction in group II (15 +/- 2.5 versus 71.3 +/- 14.5; P &lt; .02) and group III (11.4 +/- 2.5 versus 80.5 +/- 11.4; P &lt; .01) and was borderline in group IV (7.4 +/- 1.8 versus 14.1 +/- 7.4; P = .05), respectively. The incidence of macroscopic mural thrombus formation with local and systemic treatment was 86% and 75% in group I, 16% and 70% in group II, 14% and 71% in group III, and 0% and 16% in group IV, respectively. CONCLUSIONS Local therapy with the specific thrombin inhibitor r-hirudin significantly reduces short-term quantitative platelet deposition and macroscopic mural thrombus formation following balloon angioplasty compared with systemic treatment of conventional doses of heparin and hirudin and requires a significantly smaller amount of the recombinant drug.
S<scp>ARCOPENIA</scp>, W<scp>EIGHT</scp> L<scp>OSS</scp>, <scp>AND</scp> N<scp>UTRITIONAL</scp> F<scp>RAILTY IN THE</scp> E<scp>LDERLY</scp>
Authors: Connie W. Bales, Christine S. Ritchie
Journal: Annual Review of Nutrition (2002)

▪ Abstract The progression of the aging process leads to a decreased margin of homeostatic reserve and a reduced ability to accommodate metabolic challenges, including nutritional stress. Nutritional frailty refers to the disability that occurs in old age owing to rapid, unintentional loss of body weight and loss of lean body mass (sarcopenia). Sarcopenia, a loss of muscle mass and strength, contributes to functional impairment. Weight loss is commonly due to a reduction in food intake; its possible etiology includes a host of physiological and nonphysiological causes. The release of cytokines during chronic disease may also be an important determinant of frailty. In addition to being anorectic, cytokines also contribute to lipolysis, muscle protein breakdown, and nitrogen loss. Whereas the multiple causes of nutritional frailty are not completely understood, clinical interventions for weight loss, sarcopenia, and cytokine alterations have been used with modest success.
Eleven distinct VH gene families and additional patterns of sequence variation suggest a high degree of immunoglobulin gene complexity in a lower vertebrate, Xenopus laevis.
Authors: R N Haire, C T Amemiya, D Suzuki, G W Litman
Journal: The Journal of Experimental Medicine (1990)

Lower vertebrate species, including Xenopus laevis, exhibit restricted antibody diversity relative to higher vertebrates. We have analyzed more than 180 VH gene-containing recombinant clones from an unamplified spleen cDNA library by selective sequencing of JH and CH positive clones following iterative hybridization screening with family-specific VH probes, 11 unique families of VH genes, each associated with a unique genomic Southern blot hybridization pattern, are described and compared. Considerable variation in the number of hybridizing components detected by each probe is evident. The nucleotide sequence difference between VH families is as great as, if not more than, that reported in other systems, including representatives of the mammalian, avian, and elasmobranch lineages. Some Xenopus Ig gene families encode alternative amino acids at positions that are otherwise invariant or very rarely substituted in known Igs. Furthermore, variations in complementarity determining region sequences among members of the same gene family and high degrees of DH and JH region complexity are described, suggesting that in at least this lower vertebrate species, the diversity of expressed Ig VH genes is not restricted.
The Dietary Charred Meat Carcinogen 2-Amino-1-Methyl-6-Phenylimidazo[4,5-<i>b</i>]Pyridine Acts as Both a Tumor Initiator and Promoter in the Rat Ventral Prostate
Authors: Yasutomo Nakai, William G. Nelson, Angelo M. De Marzo
Journal: Cancer Research (2007)

Abstract Exposure of Fisher344 rats to 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a heterocyclic amine in cooked meat, causes cancer in the rat ventral prostate, while sparing the dorsolateral and anterior lobes. Uncovering the molecular mechanisms of the lobe specificity of PhIP-induced rat prostate cancer may provide clues to the pathogenesis of human prostate cancer, which is also lobe selective. We examined the prostate and other organs for mutation frequencies using transgenic Fisher344 rats (Big Blue rats) after PhIP treatment. After PhIP treatment for as early as 4 weeks, the colon, spleen, seminal vesicles, and all lobes of the prostate had significantly elevated mutation frequencies compared with the saline-treated control group, and the differences became even greater after 8 weeks. G:C → T:A transversions were the predominant type of mutation. After 8 weeks of treatment with PhIP, the Ki-67 index was increased (P &amp;lt; 0.001) in the ventral prostate, but not in the dorsolateral or anterior prostate. An increase in the number of stromal mast cells and macrophages was seen in the ventral prostate, but not in the other prostatic lobes. The apoptotic index also increased in the ventral lobe only. The increased proliferation and cell death in response to PhIP indicates that in addition to PhIP acting as an “initiator” of cancer, PhIP is also acting like an organ- and lobe-specific tumor “promoter.” The prostate lobe-specific infiltration of mast cells and macrophages in response to PhIP suggests a potential new mechanism by which this dietary compound can increase cancer risk—by prompting inflammation. [Cancer Res 2007;67(3):1378–84]
International Union of Basic and Clinical Pharmacology. XCVIII. Histamine Receptors
Authors: Pertti Panula, Paul L. Chazot, Marlon Cowart, Ralf Gutzmer, Rob Leurs, Wai L. S. Liu, Holger Stark, Robin L. Thurmond, Helmut L. Haas
Journal: Pharmacological Reviews (2015)

Histamine is a developmentally highly conserved autacoid found in most vertebrate tissues. Its physiological functions are mediated by four 7-transmembrane G protein-coupled receptors (H1R, H2R, H3R, H4R) that are all targets of pharmacological intervention. The receptors display molecular heterogeneity and constitutive activity. H1R antagonists are long known antiallergic and sedating drugs, whereas the H2R was identified in the 1970s and led to the development of H2R-antagonists that revolutionized stomach ulcer treatment. The crystal structure of ligand-bound H1R has rendered it possible to design new ligands with novel properties. The H3R is an autoreceptor and heteroreceptor providing negative feedback on histaminergic and inhibition on other neurons. A block of these actions promotes waking. The H4R occurs on immuncompetent cells and the development of anti-inflammatory drugs is anticipated.
PROLIFERATIVE RESPONSE OF THE SPLEEN AND LIVER TO HEMOLYSIS
Authors: James H. Jandl, Nancye M. Files, Susan Bell Barnett, Richard A. MacDonald
Journal: The Journal of Experimental Medicine (1965)

Combined chemical and autoradiographic studies in rats injected with tritiated thymidine indicate that acute red cell sequestration stimulates reticuloendothelial (RE) proliferation. In the spleen DNA synthesis is most markedly stimulated in the marginal zone which is also the initial site of red cell sequestration. This proliferative response involves several division steps and eventuates in a colonization of the red pulp with increased numbers of all cell lines native to the spleen. In both spleen and liver there occurs also a generalized stimulation of division in the macrophages and littoral cells which involves only 1 or 2 division steps. Chronic compensated hemolytic anemia achieved in rats by injections of phenylhydrazine caused functional overactivity of the RE system, including increased sequestering function and hypergammaglobulinemia. This splenic hyperplasia did not entirely regress after cessation of the injections. In man the splenomegaly of a chronic non-immunological hemolytic anemia, hereditary spherocytosis, was found to involve a marked (average: 8-fold) hyperplasia of all spleen cellular elements. Neither the acute nor chronic proliferative reaction appears to arise from immunological or "toxic" stimuli and the findings support the view that the size of the RE system is a function of its particulate "work load." It is suggested that the cytoproliferative aspects of immune responses may depend upon non-specific, usually particulate stimulation. After prolonged stimulation, hyperplasia of the RES may become partly irreversible.
Cortisol Feedback During the HPA Quiescent Period in Patients With Major Depression
Authors: Joel A. Posener, Charles DeBattista, Gordon H. Williams, Alan F. Schatzberg
Journal: American Journal of Psychiatry (2001)

The authors tested the hypothesis that patients with major depression have a defect in the mechanism by which cortisol exerts negative feedback on the hypothalamic-pituitary-adrenal (HPA) axis during the HPA axis quiescent period.Twenty-nine patients with major depression and 25 healthy comparison subjects were randomly assigned to administration of 15 mg cortisol or placebo infused over 2 hours beginning at 7:00 p.m. Cortisol and ACTH levels were measured at baseline and every 30 minutes from 7:30 p.m. to 11:00 p.m.Differences between the patients and the comparison subjects in the ACTH response to the cortisol infusion, relative to the ACTH response to placebo, were not found.The results provide some evidence that patients with major depression do not have an abnormality of cortisol feedback during the HPA axis quiescent period.