Submucosal gland secretions in airways from cystic fibrosis patients have normal [Na+] and pH but elevated viscosity

Fluid and macromolecule secretion by submucosal glands in mammalian airways is believed to be important in normal airway physiology and in the pathophysiology of cystic fibrosis (CF). An in situ fluorescence method was applied to measure the ionic composition and viscosity of freshly secreted fluid from airway glands. Fragments of human large airways obtained at the time of lung transplantation were mounted in a humidified perfusion chamber and the mucosal surface was covered by a thin layer of oil. Individual droplets of secreted fluid were microinjected with fluorescent indicators for measurement of [Na+], [Cl−], and pH by ratio imaging fluorescence microscopy and viscosity by fluorescence recovery after photobleaching. After carbachol stimulation, 0.1–0.5 μl of fluid accumulated in spherical droplets at gland orifices in ≈3–5 min. In gland fluid from normal human airways, [Na+] was 94 ± 8 mM, [Cl−] was 92 ± 12 mM, and pH was 6.97 ± 0.06 (SE, n = 7 humans, more than five glands studied per sample). Apparent fluid viscosity was 2.7 ± 0.3-fold greater than that of saline. Neither [Na+] nor pH differed in gland fluid from CF airways, but viscosity was significantly elevated by ≈2-fold compared to normal airways. These results represent the first direct measurements of ionic composition and viscosity in uncontaminated human gland secretions and indicate similar [Na+], [Cl−], and pH to that in the airway surface liquid. The elevated gland fluid viscosity in CF may be an important factor promoting bacterial colonization and airway disease.

Letter from Caleb Gannett to Eliphalet Pearson, 6 December 1804

College steward Caleb Gannett wrote this letter to interim Harvard president Eliphalet Pearson outlining supply and labor needs for an on-time completion of the new college, Stoughton Hall, in Spring 1805. Supplies include lumber for staircases, corners, and doors; lime and hair for masonry; window weights, oil, paint, nails, hinges, and locks. Gannett also requests the services of a workman to complete a coating for the roof.

Journal of College Disorders, 1788-1797

This journal contains entries about various student "disorders" which occurred during Eliphalet Pearson’s tenure at Harvard. Daily entries describe a wide range of students’ rebellious conduct, which included: hissing at speakers in chapel, throwing snowballs and stones at College buildings and people (including tutors and then-President Joseph Willard), disrupting lectures by scraping chairs and feet, breaking windows, intoxication, moving and breaking furniture, stealing firewood, firing pistols, building bonfires, stealing supplies (food, cider and candles), throwing food and utensils during meals, stealing Bibles, wearing hats indoors, filling door locks with stones, drawing on lecture room walls with gravel, and silencing the morning chapel bell by filling it with molten pewter plates (stolen from the kitchen). There are also entries pertaining to more malicious offenses, including the drowning of a dog in a well. Several entries describe meetings of the College government to determine the appropriate punishments for each offense. Students were often fined, expelled, or suspended ("rusticated") for their unruly behavior.

The old copper culture and the Keweenaw Waterway / George I. Quimby -- and Albert C. Spaulding --.

v.36:no.8(1957)

Report of the Michigan Academy of Science.

1907

Report of the Michigan Academy of Science.

1904

Report of the Michigan Academy of Science.

1901

Report of the Michigan Academy of Science.

1900

Account book of Andrew Croswell, 1794-1802

Andrew Croswell kept this account book while an undergraduate at Harvard College. It contains entries from 1794, the year he entered, until his graduation in 1798. There is also one entry on the back cover apparently made in 1802. The entries, divided by school term, are very detailed. Croswell indicates the cost of the following, among many other expenses and purchases: transportation, most often to Hingham and Plymouth; payment for "passing the bridge"; candles; hiring a horse; wood and having it cut; laundry; quills and pencils; paper and ink; razors, haircuts, hair ribbons; a trunk; clothing and cloth for trousers; furniture; tickets to the theater; door locks; a bowl and spoon; "batts and balls" and "other necessaries"; tobacco; toothbrushes; shoe and boot repair; fruit; wine, brandy and rum; cheese; coffee and tea; butter; lemons; sugar; and wafers. There are also entries for college-related costs, including the payment of quarter bills, buttery bills, Hasty Pudding Club dues, and a fee to the President of Harvard College related to Croswell's graduation. There are also entries pertaining to the cost of celebrating various special occasions, including Election Day, Christmas Eve, "Independent Day," and George Washington's birthday.

Erie Canal, New York, 1821 (Raster Image) (Image 1 of 2)

This layer is a georeferenced raster image of the historic paper map entitled: A new map and profile of the proposed canal from Lake Erie to Hudson River in the state of New York, contracted by direction of the Canal Commissioners from the maps of the engineers. It was printed by W. A. Mercein in 1821. Scale [1:253,440]. This layer is image 1 of 2 total images of the two sheet source map, representing the eastern portion of the map. The image inside the map neatline is georeferenced to the surface of the earth and fit to the Universal Transverse Mercator (UTM) Zone 18N NAD83 projection. All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as roads, drainage, cities and towns, county boundaries, and more. Relief is shown by hachures. Includes inset profiles: A profile of the extent of the levels and of the places and lifts of the locks between Lake Erie and the Hudson -- A profile of the southern route west of the Genesee River. Includes table of distances. This layer is part of a selection of digitally scanned and georeferenced historic maps from The Harvard Map Collection as part of the Imaging the Urban Environment project. Maps selected for this project represent major urban areas and cities of the world, at various time periods. These maps typically portray both natural and manmade features at a large scale. The selection represents a range of regions, originators, ground condition dates, scales, and purposes.

Erie Canal, New York, 1821 (Raster Image) (Image 2 of 2)

This layer is a georeferenced raster image of the historic paper map entitled: A new map and profile of the proposed canal from Lake Erie to Hudson River in the state of New York, contracted by direction of the Canal Commissioners from the maps of the engineers. It was printed by W. A. Mercein in 1821. Scale [1:253,440]. This layer is image 2 of 2 total images of the two sheet source map, representing the western portion of the map. The image inside the map neatline is georeferenced to the surface of the earth and fit to the Universal Transverse Mercator (UTM) Zone 18N NAD83 projection. All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as roads, drainage, cities and towns, county boundaries, and more. Relief is shown by hachures. Includes inset profiles: A profile of the extent of the levels and of the places and lifts of the locks between Lake Erie and the Hudson -- A profile of the southern route west of the Genesee River. Includes table of distances. This layer is part of a selection of digitally scanned and georeferenced historic maps from The Harvard Map Collection as part of the Imaging the Urban Environment project. Maps selected for this project represent major urban areas and cities of the world, at various time periods. These maps typically portray both natural and manmade features at a large scale. The selection represents a range of regions, originators, ground condition dates, scales, and purposes.

New Orleans, Louisiana, 1884 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Map of the city of New Orleans showing location of exposition grounds and all approaches thereto by land & water, [by] the World's Industrial and Cotton Centennial Exposition, New Orleans, La., U.S.A., Department of Installation. It was published by The Exposition ca. 1884. Scale [ca. 1:2,000]. Covers also adjacent portions of Jefferson and St. Bernard Parishes. The image inside the map neatline is georeferenced to the surface of the earth and fit to the Louisiana State Plane Coordinate System, South NAD83 (in Feet) (Fipszone 1702). All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, or other information associated with the principal map. This map shows features such as exposition grounds, railroads, roads, canals, levees, drainage, block numbers, land ownership in outlying areas, selected public and industrial buildings, cemeteries, Parish boundaries, ferry routes, and more. Depths shown by soundings. Includes inset views, plans, and engravings: Perspective view of the buildings and grounds from the Northeast -- Mexican national headquarters -- Grand Rapids (Mich.) furniture pavilion -- [South pass] -- View of New Orleans in 1719 -- Railroad map of Louisiana and Texas -- Plan of New Orleans in 1770 by Capt.n Pittman of the British Army -- Ground plan -- United States and state exhibits -- Art gallery -- Main building -- Factories and Mills -- Horticultural hall. This layer is part of a selection of digitally scanned and georeferenced historic maps from The Harvard Map Collection as part of the Imaging the Urban Environment project. Maps selected for this project represent major urban areas and cities of the world, at various time periods. These maps typically portray both natural and manmade features at a large scale. The selection represents a range of regions, originators, ground condition dates, scales, and purposes.

Drug-induced torsades de pointes in an underserved urban population. Methadone: is there therapeutic equipoise?

BACKGROUND Although it has been well established that methadone use can result in prolonged QTc/torsades de pointes (TdP) and has been labeled as one of the main drugs that cause TdP, it is still prescribed indiscriminately, and several cases of methadone-associated TdP have been seen in our community. METHODS Our objective was to determine the associated factors for prolonged QTc and the development of torsades de pointes (TdP) in our underserved patient population. We found 12,550 ECGs with prolonged QTc between 2002 and 2013. Medical records were reviewed in order to identify precipitating factors for prolonged QTc and to detect incidence of TdP. RESULTS We identified 2735 patients with prolonged QTc who met the inclusion criteria. Of these, 89 (3%) experienced TdP. There was a greater prevalence of HIV infection in the TdP group (11.2 vs. 3.7%, p < 0.001). Furosemide, hydrochlorothiazide, selective serotonin reuptake inhibitors (SSRIs), amiodarone, ciprofloxacin, methadone, haloperidol, and azithromycin were the drugs most often associated with prolonged QTc (31, 8.2, 7.6, 7.1, 3.9, 3.4 and 3.3%, respectively). However, the agents most commonly associated with TdP were furosemide (39.3%), methadone (27%), SSRIs (19.1%), amiodarone (18%), and dofetilide (9%). The medications with statistical significance in the multivariate analysis for TdP development in descending order were as follows: ranolazine (odds ratios [OR] = 53.61, 95% confidence interval [CI] 5.4-524, p < 0.001), dofetilide (OR = 25, CI 6.47-103.16, p < 0.001), voriconazole (OR = 21.40, CI 3.24-124.25, p < 0.001), verapamil (OR = 10.98, CI 2.62-44.96, p < 0.001), sotalol (OR = 12.72, 1.95-82.81, p = 0.008), methadone (OR = 9.89, CI 4.05-24.15, p < 0.001), and SSRI (OR = 2.26, CI 1.10-5.96, p < 0.001). This multivariate analysis revealed that amiodarone and HIV infection were not implicated in TdP. CONCLUSION Methadone was by far the leading medication implicated in the development of TdP and an independent predictor in both univariate and multivariate analyses despite the fact that it was not the most common QT-prolonging medication in our population.