Mass law predicts hyperbolic hypoxic ventilatory response.
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Biomedical subjects
Publications and source records attributed to John W Severinghaus.
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We examined the effect of dietary supplementation with L-arginine on breath condensate VEGF, exhaled nitric oxide (NO), plasma erythropoietin, symptoms of acute mountain sickness, and respiratory related sensations at 4,342 m through the course of 24 h in seven healthy male subjects. Serum L-arginine levels increased in treated subjects at time 0, 8, and 24 h compared with placebo, indicating the effectiveness of our treatment. L-arginine had no significant effect on overall Lake Louise scores compared with placebo. However, there was a significant increase in headache within the L-arginine treatment group at 12 h compared with time 0, a change not seen in the placebo condition between these two time points. There was a trend (p = 0.087) toward greater exhaled NO and significant increases in breath condensate VEGF with L-arginine treatment, but no L-arginine effect on serum EPO. These results suggest that L-arginine supplementation increases HIF-1 stabilization in the lung, possibly through a NO-dependent pathway. In total, our observations indicate that L-arginine supplementation is not beneficial in the prophylactic treatment of AMS.
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BACKGROUND: It is uncertain whether skin pigmentation affects pulse oximeter accuracy at low HbO2 saturation. METHODS: The accuracy of finger pulse oximeters during stable, plateau levels of arterial oxygen saturation (Sao2) between 60 and 100% were evaluated in 11 subjects with darkly pigmented skin and in 10 with light skin pigmentation. Oximeters tested were the Nellcor N-595 with the OxiMax-A probe (Nellcor Inc., Pleasanton, CA), the Novametrix 513 (Novametrix Inc., Wallingford, CT), and the Nonin Onyx (Nonin Inc., Plymouth, MN). Semisupine subjects breathed air-nitrogen-carbon dioxide mixtures through a mouthpiece. A computer used end-tidal oxygen and carbon dioxide concentrations determined by mass spectrometry to estimate breath-by-breath Sao2, from which an operator adjusted inspired gas to rapidly achieve 2- to 3-min stable plateaus of desaturation. Comparisons of oxygen saturation measured by pulse oximetry (Spo2) with Sao2 (by Radiometer OSM3) were used in a multivariate model to determine the interrelation between saturation, skin pigmentation, and oximeter bias (Spo2 - Sao2). RESULTS: At 60-70% Sao2, Spo2 (mean of three oximeters) overestimated Sao2 (bias +/- SD) by 3.56 +/- 2.45% (n = 29) in darkly pigmented subjects, compared with 0.37 +/- 3.20% (n = 58) in lightly pigmented subjects (P < 0.0001). The SD of bias was not greater with dark than light skin. The dark-light skin differences at 60-70% Sao2 were 2.35% (Nonin), 3.38% (Novametrix), and 4.30% (Nellcor). Skin pigment-related differences were significant with Nonin below 70% Sao2, with Novametrix below 90%, and with Nellcor at all ranges. Pigment-related bias increased approximately in proportion to desaturation. CONCLUSIONS: The three tested pulse oximeters overestimated arterial oxygen saturation during hypoxia in dark-skinned individuals.
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OBJECTIVE: To investigate an unexpectedly high initial skin CO2 pressure with a new small earlobe probe* heated to 42 degrees C containing both transcutaneous (tcPCO2) and pulse oximeter saturation (SpO2) sensors. METHODS: The probe was mounted on the ear lobe of six patients during abdominal or thoracic surgery and on several awake volunteers. The probe was mounted on a cheek or forearm in two other volunteers. Patients were artificially ventilated under general anesthesia at constant end-expiratory PCO2. RESULTS: In patients, at 8 +/- 3 min after mounting, tcPCO2 peaked 5 mmHg higher than its final value (p = 0.0067, n = 6, paired t-test). After 25 min, tcPCO2 was not different from PaCO2 (arterial). Similar overshoots were recorded with this device when mounted on the arm or cheek and with a standard transcutaneous PCO2 probe set to 42 degrees C, mounted on the ear lobe, arm or chest of awake volunteers. In two volunteers, we found that heating the sensor to 45 degrees C for the first 15 min on the ear, and then decreasing it to 42 degrees C prevented overshoot, and provided valid tcPCO2 data 3 - 5 min after application of the sensor. CONCLUSIONS: A temperature of 42 degrees C may increase local skin temperature and metabolism before vasodilating more remote arteriolar control of sub-sensor capillary flow. We suggest that transcutaneous PCO2 probes be initially set to 44 - 45 degrees C for 5 - 15 min to induce prompt vasodilation to prevent this overshoot and then reduced to 42 degrees C to avoid skin thermal injury in case of long-term application.
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Americans are taught that Joseph Priestley discovered oxygen in 1774 and promptly brought that news to Lavoisier. Lavoisier proved that air contained a new element, oxygen, which combined with hydrogen to make water. He disproved the phlogiston theory but Priestley called it dephlogisticated air until his death 30 years later. Scandanavians learn that a Swedish apothecary Carl Wilhelm Scheele beat Priestley by 2 years but was deprived of credit because Lavoisier denied receiving a letter Scheele later claimed to have sent in September 1774 describing his 1772 discovery of "fire air". His claim was unconfirmed because Scheele first published his work in 1777. However, Scheele's missing letter was made public in 1992 in Paris, 218 years late, and now resides at the French Academie de Sciences. Lavoisier received it on Oct 15, 1774. His guilt was kept secret in the effects of Madame Lavoisier. He failed on several occasions to credit either Priestley or Scheele for contributing to the most important discovery in the history of science. Priestley was a teacher, political philosopher, essayist, Unitarian minister and pioneer in chemical and electrical science. He discovered 9 gases including nitrous oxide. He invented soda water, refrigeration, and gum erasers for which he coined the term "rubber". He discovered photosynthesis. He was humorless, argumentative, brilliant and passionate, called a "furious free-thinker". While his liberal colleagues Josiah Wedgwood, Erasmus Darwin, James Watts, and others of the Lunar Society were celebrating the 2nd anniversary of the French revolution, a Birmingham mob, supported by the royalists and the established church, destroyed Priestley's home, laboratory and church. Driven from England, he emigrated to Pennsylvania where he built a home and laboratory and collected a 1600 volume library, then among the largest in America. He is regarded as a founder of liberal Unitarian thinking. He was friend and correspondent of Thomas Jefferson. His philosophy and insight persuaded Jefferson to initiate what Americans call a liberal arts education. Scheele was later recognized as a brilliant and productive pioneer in chemistry although he died at age 44 of tasting his own arsenic compounds. In the new time-lapse play "Oxygen" set in Stockholm in both 18th and 21st centuries, in 1774, blame falls on Lavoisier's wife who hid Scheele's letter in hopes of giving her husband sole credit for discovering oxygen. In 2001, four Nobel committee panelists cannot agree which should receive the first "Retro-Nobel Prize" for the greatest discovery of all time: Priestley, Scheele or Lavoisier or all three. The audience is asked to choose.
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In 1953, the doctor draft interrupted Dr. Severinghaus' anesthesia and physiology training and sent him to the National Institutes of Health as director of anesthesia research at the newly opened Clinical Center. He developed precise laboratory partial pressure of carbon dioxide (PCO(2)) and pH analysis to investigate lung blood gas exchange during hypothermia. Constants for carbon dioxide solubility and pK' were more accurately determined. In August 1954, he heard Richard Stow describe invention of a carbon dioxide electrode and immediately built one, improved its stability, and tested its response characteristics. In April 1956, he also heard Leland Clark reveal his invention of an oxygen electrode. Dr. Severinghaus obtained one and constructed a stirred cuvette in which blood partial pressure of oxygen (PO(2)) could be accurately measured. Technician Bradley and Dr. Severinghaus combined these, making the first blood gas analysis system in 1957 and 1958, and shortly thereafter, they added a pH electrode. Blood gas analyzers rapidly developed commercially. Dr. Severinghaus collaborated with Astrup and other Danes on the Haldane and Bohr effects and their concepts of base excess during two sabbaticals in Copenhagen. Work with both Astrup and Roughton on the oxygen dissociation curve led Dr. Severinghaus to devise a modified Hill equation that closely fit their new, better human oxygen dissociation curve and a blood gas slide rule that solved oxygen dissociation curve, PCO(2), pH, and acid-base questions. Blood gas analysis revolutionized both clinical medicine and cardiorespiratory and metabolic physiology.