tbuckley/cabot-search huggingface dataset:
The efficacy of octreotide in the therapy of severe nonproliferative and early proliferative diabetic retinopathy: a randomized controlled study.
Authors: M B Grant, R N Mames, C Fitzgerald, K M Hazariwala, R Cooper-DeHoff, S Caballero, K S Estes
Journal: Diabetes Care (2000)

The pilot study examined the ability of octreotide to retard progression of diabetic retinopathy (DR) and delay the need for panretinal photocoagulation (PRP) in patients with advanced stages of retinal disease.Patients with severe nonproliferative DR (NPDR) or early non-high-risk proliferative DR (PDR) were randomly assigned to conventional diabetes management (control group, 12 patients) or to treatment with maximally tolerated doses of octreotide (200-5,000 microg/day subcutaneously; 11 patients). Ocular changes in each eye were assessed at a minimum of every 3 months for 15 months or until disease progressed to high-risk PDR requiring laser surgery. Endocrine assessments occurred at 3-month intervals during the studyOnly 1 of 22 eyes from patients treated with octreotide reached high-risk PDR requiring PRP, compared with control patients, in whom 9 of 24 eyes required PRP. The decreased incidence of progression requiring laser surgery was statistically significant if events were considered independently (P < 0.006). The incidence of ocular disease progression was only 27% in patients treated with octreotide compared with 42% in patients with conventional diabetes management. This treatment effect on whether the retina worsened approached statistical significance using repeated measures analysis (P = 0.0605). Endocrine management was similar between treatment groups. Thyroxine replacement therapy was administered to maintain a euthyroid state for all octreotide-treated patients and 7 of 12 control patients.Our results suggest that octreotide treatment in euthyroid patients may retard progression of advanced DR and may delay the time to laser surgery.
Using Laboratory Models to Test Treatment
Authors: Robert B. Banzett, Lewis Adams, Carl R. O'Donnell, Sean A. Gilman, Robert W. Lansing, Richard M. Schwartzstein
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Rationale: Opioids are commonly used to relieve dyspnea, but clinical data are mixed and practice varies widely.Objectives: Evaluate the effect of morphine on dyspnea and ventilatory drive under well-controlled laboratory conditions.Methods: Six healthy volunteers received morphine (0.07 mg/kg) and placebo intravenously on separate days (randomized, blinded). We measured two responses to a CO2 stimulus: (1) perceptual response (breathing discomfort; described by subjects as "air hunger") induced by increasing partial pressure of end-tidal carbon dioxide (PetCO2) during restricted ventilation, measured with a visual analog scale (range, "neutral" to "intolerable"); and (2) ventilatory response, measured in separate trials during unrestricted breathing.Measurements and Main Results: We determined the PetCO2 that produced a 60% breathing discomfort rating in each subject before morphine (median, 8.5 mm Hg above resting PetCO2). At the same PetCO2 after morphine administration, median breathing discomfort was reduced by 65% of its pretreatment value; P < 0.001. Ventilation fell 28% at the same PetCO2; P < 0.01. The effect of morphine on breathing discomfort was not significantly correlated with the effect on ventilatory response. Placebo had no effect.Conclusions: (1) A moderate morphine dose produced substantial relief of laboratory dyspnea, with a smaller reduction of ventilation. (2) In contrast to an earlier laboratory model of breathing effort, this laboratory model of air hunger established a highly significant treatment effect consistent in magnitude with clinical studies of opioids. Laboratory studies require fewer subjects and enable physiological measurements that are difficult to make in a clinical setting. Within-subject comparison of the response to carefully controlled laboratory stimuli can be an efficient means to optimize treatments before clinical trials.
Cardiac AAV9 Gene Delivery Strategies in Adult Canines: Assessment by Long-term Serial SPECT Imaging of Sodium Iodide Symporter Expression
Authors: Gilles Moulay, Tomohito Ohtani, Ozgur Ogut, Adam Guenzel, Atta Behfar, Rosita Zakeri, Philip Haines, Jimmy Storlie, Lorna Bowen, Linh Pham, David Kaye, Gurpreet Sandhu, Michael O’Connor, Stephen Russell, Margaret Redfield
Journal: Molecular Therapy (2015)

Heart failure is a leading cause of morbidity and mortality, and cardiac gene delivery has the potential to provide novel therapeutic approaches. Adeno-associated virus serotype 9 (AAV9) transduces the rodent heart efficiently, but cardiotropism, immune tolerance, and optimal delivery strategies in large animals are unclear. In this study, an AAV9 vector encoding canine sodium iodide symporter (NIS) was administered to adult immunocompetent dogs via epicardial injection, coronary infusion without and with cardiac recirculation, or endocardial injection via a novel catheter with curved needle and both end- and side-holes. As NIS mediates cellular uptake of clinical radioisotopes, expression was tracked by single-photon emission computerized tomography (SPECT) imaging in addition to Western blot and immunohistochemistry. Direct epicardial or endocardial injection resulted in strong cardiac expression, whereas expression after intracoronary infusion or cardiac recirculation was undetectable. A threshold myocardial injection dose that provides robust nonimmunogenic expression was identified. The extent of transmural myocardial expression was greater with the novel catheter versus straight end-hole needle delivery. Furthermore, the authors demonstrate that cardiac NIS reporter gene expression and duration can be quantified using serial noninvasive SPECT imaging up to 1 year after vector administration. These data are relevant to efforts to develop cardiac gene delivery as heart failure therapy.
New insights on the mechanisms of valproate-induced hyperammonemia: Inhibition of hepatic N-acetylglutamate synthase activity by valproyl-CoA
Authors: Cátia C.P. Aires, Arno van Cruchten, Lodewijk IJlst, Isabel Tavares de Almeida, Marinus Duran, Ronald J.A. Wanders, Margarida F.B. Silva
Journal: Journal of Hepatology (2010)
[609] TELAPREVIR (VX 950)-RESISTANT VARIANTS EXHIBIT REDUCED REPLICATION CAPACITY COMPARED TO WILD-TYPE HCV IN VIVO AND IN VITRO
Authors: H.-M. Chu, Y. Zhou, D.T. Bartels, A. Khunvichai, B.G. Rao, A.D. Kwong, C. Lin
Journal: Journal of Hepatology (2007)
Press: Lifting a smokescreen
Authors: A. Moscrop
Journal: BMJ (2001)

Is the women and tobacco campaign a ploy to promote smoking cessation products?

Women and smoking was the subject of a swirl of media attention last week. Striking tabloid images showed the impact of smoking on women's appearance. Alongside “shocking pictures,” the Daily Express explained that “experts from taskforce SCAPE (Smoking Cessation Action in Primary carE) artificially aged a pair of identical twins to show how they might look at the age of 40 if one continues to smoke and the other remains a non-smoker.” There was no explanation of what SCAPE is or what prompted its publicity stunt. Television news provided greater insight. ITN reported the results of a survey recently commissioned by SCAPE: “Women don't know about the risks of smoking … Nearly 99 per cent did not know of the link between smoking and cervical cancer.”

SCAPE describes itself as “a group of health care professionals, working in primary care, dedicated to driving the effective delivery …
Ischemic preconditioning reduces infarct size in swine myocardium.
Authors: R J Schott, S Rohmann, E R Braun, W Schaper
Journal: Circulation Research (1990)

We evaluated the hypothesis that stunning swine myocardium with brief ischemia reduces oxygen demand in the stunned region and increases tolerance of myocardium to longer periods of ischemia. Wall function was quantified with ultrasonic crystals aligned to measure wall thickening, and stunning was achieved with two cycles of left anterior descending coronary artery (LAD) occlusion (10 minutes) and reperfusion (30 minutes), after which the LAD was occluded for 60 minutes and reperfused for 90 minutes. Infarct size (as a percent of risk region) was then determined by incubating myocardium with para-nitro blue tetrazolium. Regional oxygen demand was measured as myocardial oxygen consumption before the 60-minute LAD occlusion in the stunned region; tracer microspheres were used to determine blood flow, and blood from the anterior interventricular vein and left atrium was used to calculate oxygen saturations. After the second reperfusion period, wall thickening in the stunned region was reduced to 1.4 +/- 2.4% compared with 36.7 +/- 2.5% (mean +/- SEM) before ischemia (p less than 0.001). Regional myocardial oxygen consumption after stunning (3.1 +/- 0.7 ml O2/min/100 g) was no different from regional myocardial oxygen consumption before stunning (3.7 +/- 0.6 ml O2/min/100 g). In the nine pigs "preconditioned" by stunning, infarct size was 10.4 +/- 6.3% of the risk region compared with 48.0 +/- 12.7% in the six control pigs subjected to 60 minutes of ischemia without prior stunning (p less than 0.005). The risk regions were similar (14.4 +/- 1.5% vs. 14.6 +/- 1.9% of the left ventricle, preconditioned vs. control pigs, respectively). We conclude that stunning swine myocardium with two cycles of a 10-minute LAD occlusion followed by reperfusion increases ischemic tolerance but that changes in regional demand in stunned myocardium do not predict the marked reduction in infarct size that follows a subsequent 60-minute period of ischemia.
Vitamin D in patients on anticonvulsants.
Authors: J Linde, J M Hansen, K Siersbaek-Nielsen, V Fuglsang-Frederiksen
Journal: BMJ (1972)

powerful antibiotic is sufficient without drainage of an abscess."I would like to question this statement.I have personally cleared out more than one sterile cavity persisting several months after the apparent cure of osteomyelitis with antibiotics alone.-I am, etc., R. MERRYWEATHER Gloucester Vitamin D in Patients on Anticonvulsants SIR,-Dr.Claus Christiansen and others (23 September, p. 738) showed an increase in bone density during treatment with vitamin D in 10 epileptic patients on anticonvulsants.We have previously shown significantly lower values of bone density in a group of nine epileptic women compared with a con- trol group of 10 psychiatric patients resident in the same epileptic colony.'After our initial investigation in June 1971 we reinvestigated our groups of patients in Febru- ary 1972 to find out if there was a seasonal variation in bone density values, but they were unaltered.During the next six months both groups were given calciferol 50,000 IU/day by mouth.Bone density was assessed by gamma-ray osteodensitometry after three and six months of vitamin D treatment.During vitamin D treatment no significant alteration in bone density could be demonstrated, but bone density mean values measured both on the heel and elbow remained significantly lower in the group of epileptic patients.None of the patients showed signs of vitamin D overdosage.The discrepancy between our results and those of Dr. Christiansen and his colleagues mittht be explained by differences in the epileptics studied with respect to sex, age, duration of anticonvulsant therapy, vitamin D dosage, and calcium intake.We are making further studies of bone density in epileptic patients on anticonvulsants during treatment with vitamin D and calcium.-We
Forms and prevalence of intersexuality and effects of environmental contaminants on sexuality in cricket frogs (Acris crepitans).
Authors: A L Reeder, G L Foley, D K Nichols, L G Hansen, B Wikoff, S Faeh, J Eisold, M B Wheeler, R Warner, J E Murphy, V R Beasley
Journal: Environmental Health Perspectives (1998)

Cricket frogs (Acris crepitans) from several different sites in Illinois were collected to assess the effects of environmental contamination on the prevalence of intersex gonads. Of 341 frogs collected in 1993, 1994, and 1995, 2.7% were intersex individuals. There was no statistically significant relationship between the chemical compounds detected and cricket frog intersexuality. However, there was an association approaching significance (p = 0.07) between the detection of atrazine and intersex individuals. A comparison of reference sites with sites that had point polychlorinated biphenyl (PCB) and polychlorinated dibenzofuran (PCDF) contamination revealed a significant relationship between sex-ratio reversal and contamination with PCBs and PCDFs. The sex ratio of juvenile frogs studied from three sites with PCB and PCDF point contamination favored males over females, which was the opposite of the sex ratio in control ponds (p = 0.0007). The statistically significant correlation between organochlorine contamination and sex-ratio reversal suggests PCBs and PCDFs can influence cricket frog sexual differentiation. The current study suggests that in cricket frogs, sex ratios and the prevalence of intersex gonads are altered by environmental contamination.
Mossy Fiber-CA3 Synapses Mediate Homeostatic Plasticity in Mature Hippocampal Neurons
Authors: Kea Joo Lee, Bridget N. Queenan, Aaron M. Rozeboom, Ryan Bellmore, Seung T. Lim, Stefano Vicini, Daniel T.S. Pak
Journal: Neuron (2013)

Network activity homeostatically alters synaptic efficacy to constrain neuronal output. However, it is unclear how such compensatory adaptations coexist with synaptic information storage, especially in established networks. Here, we report that in mature hippocampal neurons in vitro, network activity preferentially regulated excitatory synapses within the proximal dendrites of CA3 neurons. These homeostatic synapses exhibited morphological, functional, and molecular signatures of the specialized contacts between mossy fibers of dentate granule cells and thorny excrescences (TEs) of CA3 pyramidal neurons. In vivo TEs were also selectively and bidirectionally altered by chronic activity changes. TE formation required presynaptic synaptoporin and was suppressed by the activity-inducible kinase, Plk2. These results implicate the mossy fiber-TE synapse as an independently tunable gain control locus that permits efficacious homeostatic adjustment of mossy fiber-CA3 synapses, while preserving synaptic weights that may encode information elsewhere within the mature hippocampal circuit.
PROGNOSTIC ROLE OF N-TERMINAL PRO-BRAIN NATRIURETIC PEPTIDE IN A POPULATION AT HIGH RISK FOR CARDIOVASCULAR DISEASE.
Authors: Irene Betti, Piercarlo Ballo, Alessandro Barchielli, Alfredo Zuppiroli, Unità Operativa di Cardiologia, Ospedale S. Maria Annunziata
Journal: Journal of the American College of Cardiology (2010)
Hepatitis C virus (HCV) infection and cryoglobulinemia: Analysis of whole blood and plasma HCV-RNA concentrations and correlation with liver histology
Authors: Warren N. Schmidt, Jack T. Stapleton, Douglas R. LaBrecque, Frank A. Mitros, Patricia A. Kirby, Mary Jeanne Perino Phillips, Donna L. Brashear
Journal: Hepatology (2000)

The influence of cryoprecipitate (CP) on liver histology and peripheral titers of hepatitis C virus (HCV) RNA was evaluated for 115 patients with chronic hepatitis. Fifty-four patients had measurable CP levels whereas 61 did not. Assessment of liver biopsies for grade of fibrosis revealed that patients with CP had increased fibrosis ( P &lt; .001) and incidence of cirrhosis ( P = .001) compared with those without CP. In contrast, there was not a significant difference in the inflammatory activity score between the 2 groups. HCV RNA in whole blood (WB) and plasma (Pl) was evaluated in patients with or without CP by end-point-limiting dilution titer. Among patients with CP, WB titers were significantly higher than Pl titers ( P &lt; .001); however, there was no difference in WB or Pl titers in patients without CP ( P = .068). Histological activity and fibrosis scores of patients from either group were compared with peripheral viral titers of WB and Pl, percentage of CP, rheumatoid factor (RF) titer, and serum alanine transaminase (ALT). There were significant correlations between the amount of fibrosis and the percentage of CP and rheumatoid factor titer, yet neither of the latter parameters was correlated with inflammatory activity. These data suggest that patients with CP and chronic hepatitis owing to HCV are more likely to have progressive disease than patients without CP. Furthermore, the presence of CP in patients infected with HCV appears to influence the amount of virus detected in patient Pl, suggesting that WB assays may be more reliable for HCV-RNA quantitation in patients with CP.
F-18 FDG Brain PET and Tc-99m ECD Brain SPECT in a Patient With Multiple Recurrent Epileptic Seizures
Authors: Sophie Turpin, Raymond Lambert, Josée Dubois, Paola Diadori
Journal: Clinical Nuclear Medicine (2010)

The combination of interictal brain fluorine-18 fluorodeoxyglucose positron emission tomography (F18-FDG PET) and ictal brain Tc-99m ethylcysteinate dimer (ECD) SPECT is currently used for identification of epileptic foci. Usually, hypometabolism is demonstrated on the F-18 FDG PET and hyperperfusion in the same region on the Tc-99m ECD ictal SPECT. The authors report a rare occurrence of left frontal hypermetabolism in a young girl with multiple recurring epileptic seizures, on F18-FDG PET, which was confirmed on ictal Tc-99m ECD SPECT. The patient's seizures were characterized by head deviation and movements of the upper extremities. The seizures were occurring non stop every 3 to 5 minutes, even during imaging, lasting about 15 seconds. Magnetic resonance imaging (MRI) showed evidence of dysplastic cortex which was consistent with the focal abnormalities on PET and SPECT.
Proliferation and hypertrophy of liver cells surrounding islet grafts in diabetic recipient rats*1
Authors: M DEPAEPE
Journal: Hepatology (1995)

The liver offers an adequate site for the metabolic function of pancreatic islet implants. Little is known about the effects of the islet grafts on the host organ. This study examines liver tissue of normal or streptozotocin (STZ)-diabetic rats at different intervals following intraportal injection of syngeneic islets. Implantation of 800-islet-grafts, containing 0.9 million beta cells, normalized overt diabetes within 14 days. This period of metabolic normalization was characterized by a specific sequence of alterations in the implant area. During the first days after transplantation, islet cells migrated into the liver lobules, whereby tight hepatocyte-islet cell contacts were established. Hepatocytes surrounding grafts showed massive lipid accumulation and hypertrophy (cellular profile area 603 +/- 72 microns 2 in diabetic islet recipients vs. 382 +/- 42 microns 2 in diabetic controls; P < .005). The implant area also contained significantly more liver cells in proliferative activity than hepatic tissue in normal controls (bromodeoxyuridine labeling index of peri-islet hepatocytes 6.2%, 4.6%, and 0.9% on posttransplantation days 2, 4, and 14, respectively, compared with 0.02% in normal controls). The cellular hypertrophy and hyperplasia explain the sudden increase in liver weight of diabetic recipients (from 8.0 +/- 1.1 g to 13.8 +/- 2.2 g on posttransplantation day 2; P < .005). Both alterations can be attributed to the massive local discharge of insulin in an insulin-deficient organ containing an excess of extra-cellular nutrients. Progressive revascularization of the implant sites and overall metabolic normalization are thought to explain the return of a normal liver histology by the third week after transplantation. In conclusion, intraportal islet grafts exert profound effects on the liver of diabetic rat recipients. The morphological features of the implant sites may serve as markers for the function of the islet grafts as well as for the adaptive capacity of the recipient liver.
Forecasting Physician Workforce Requirements
Authors: James Hallock, Edward Kobrinski, Christopher Mansfield
Journal: JAMA (1995)

To the Editor.  —Dr Weiner 1 presents an exacting analysis of the likely effects of health system reform on physician workforce requirements. His market approach to forecasting is a careful projection of physicians needed in the year 2000. He uses health maintenance organization (HMO) plans as the prototype for the managed care environment likely to come out of current reform. However, he points out that it is not very realistic to expect that managed care.. will ever serve a large proportion of rural Americans, and it is not reasonable to expect that rural areas will ever be staffed with physicians at the same levels as urban locales.... We agree with this conclusion, but wish to point out that this conclusion might be because of his emphasis on the supply side of a market-based approach.  From our perspective and experience with rural populations in North Carolina, Weiner has overlooked two important
Carotid Intima Media Thickness Predicts Cardiovascular Diseases in Chinese Predialysis Patients with Chronic Kidney Disease
Authors: Cheuk-Chun Szeto, Kai-Ming Chow, Kam-Sang Woo, Ping Chook, Bonnie Ching-Ha Kwan, Chi-Bon Leung, Philip Kam-Tao Li
Journal: Journal of the American Society of Nephrology (2007)

Patients with chronic kidney disease (CKD) have a high risk for cardiovascular disease. Ultrasound measurements of the intima media thickness (IMT) in the carotid arteries is a strong predictor for cardiovascular events in the general population and dialysis patients. However, it is unclear whether carotid IMT is useful for the prediction of cardiovascular events in predialysis patients with CKD. The prediction power of carotid ultrasonography for cardiovascular event, rate of renal function decline, and all-cause mortality was tested in a cohort of 203 Chinese patients with stages 3 to 4 CKD. The average IMT was 0.808 +/- 0.196 mm; 121 (59.6%) patients had atherosclerotic plaques visualized. IMT correlated with patient age (r = 0.373, P < 0.001), serum LDL level (r = 0.164, P = 0.021), Charlson's comorbidity score (r = 0.260, P < 0.001), and serum C-reactive protein (r = 0.279, P < 0.001). Carotid IMT was significantly higher in patients with diabetes than in those without diabetes (0.930 +/- 0.254 versus 0.794 +/- 0.184; P = 0.002). At 48 mo, the cardiovascular event-free survival was 94.4, 89.8, 77.7, and 65.9% for IMT quartiles I, II, III, and IV, respectively (log rank test, P = 0.006). By multivariate analysis with the Cox proportional hazard model, each higher quartile of IMT conferred 41.6% (95% confidence interval 6.4 to 88.4%; P = 0.017) excess hazard for developing cardiovascular event. The actuarial survival at 48 mo was 96.3, 98.0, 95.7, and 85.7% for IMT quartiles I, II, III and IV, respectively (log rank test, P = 0.127), and the difference was not statistically significant after Cox proportional hazard model to adjust for confounders. Carotid IMT did not correlate with the rate of renal function decline in these patients. Carotid IMT is a strong predictor of cardiovascular disease in Chinese predialysis patients and may be usefully applied for risk stratification in this group of patients.