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Biomedical subjects

N A Bergman

Publications and source records attributed to N A Bergman.

At least 19 recordsLinked to original sources
PubMed1995

Structure-activity relationship of omeprazole and analogues as Helicobacter pylori urease inhibitors.

Helicobacter pylori urease belongs to a family of highly conserved urea-hydrolyzing enzymes. A common feature of these enzymes is the presence of two Lewis acid nickel ions and a reactive cysteine residue in the active site. The H+/K(+)-ATPase inhibitor omeprazole is a prodrug of a sulfenamide which covalently modifies cysteine residues on the luminal side of the H+/K(+)-ATPase of gastric parietal cells. Omeprazole and eight analogues were selected based on their chemical, electronic, and kinetic properties, and each was incubated with viable H. pylori in phosphate-buffered saline at pH 7.4 for 30 min, after which 100 mM urea was added and the amount of ammonia formed analyzed after a further 10 min. Inhibition between 0% and 100% at a 0.1 mM concentration was observed for the different analogues and could be expressed as a function of the pKa-value of the pyridine, the pKa-value of the benzimidazole, the overall lipophilicity, and, most importantly, the rate of sulfenamide formation, in a quantitative structure-activity relationship. The inhibition was potentiated by a lower pH (favoring the formation of the sulfenamide) but abolished in the presence of beta-mercaptoethanol (a scavenger of the sulfenamide). Structural analogues incapable of yielding the sulfenamide did not inhibit ammonia production. Treatment of Helicobacter felis-infected mice with 230 mumol/kg flurofamide b.i.d. for 4 weeks, known to potently inhibit urease activity in vivo, as a means of eradicating the infection, was tested and compared with the effect of 125 mumol/kg omeprazole b.i.d. for 4 weeks. Neither treatment proved efficacious.

Ammonia↗
PubMed1994

William Wright, aurist: nineteenth century pneumatic practitioner and a discoverer of anesthesia.

William Wright (1773-1860) was Surgeon-Aurist in Ordinary to Her Majesty Queen Charlotte of England. One interesting feature of his otologic practice was his employment of gases and vapors in treating deafness and other disorders of the ear. Among aeroform substances that he advocated for such uses were nitrous oxide and ether--gases that were destined to become anesthetic agents in another quarter of a century. Wright made the observation that inhalation of ether vapor would suppress the cough elicited by instrumentation of an inflamed and sensitive ear canal. He used ether inhalation beginning about 1820 in his practice for this purpose, and in so doing appears to have administered some of the earliest anesthetics on record.

Anesthesia↗
PubMed1992

Michael Faraday and his contribution to anesthesia.

Michael Faraday (1791-1867) was a protégé of Humphry Davy. He became one of Davy's successors as Professor of Chemistry at the Royal Institution of Great Britain. Of Faraday's many brilliant discoveries in chemistry and physics, probably the best remembered today is his work on electromagnetic induction. Faraday's contribution to introduction of anesthesia was his published announcement in 1818 that inhalation of the vapor of ether produced the same effects on mentation and consciousness as the breathing of nitrous oxide. He most likely became familiar with the central nervous system effects of nitrous oxide through his association with Davy, an avid user of the gas. Sulfuric ether was a common, convenient, cheap, and easily available substance, in contrast to nitrous oxide, which required expensive, cumbersome, and probably not widely available apparatus for its production and administration. The capability for inhaling intoxicating vapors eventually became commonly available with the use of ether instead of the gas. The first surgical anesthetics were a consequence of the resulting student "ether frolics." The 1818 announcement on breathing ether vapor was published anonymously; however, notations in Faraday's handwriting in some of his personal books clearly establish Michael Faraday as the author of this brief communication.

Anesthesiology↗
PubMed1990

Early intravenous anesthesia: an eyewitness account.

Descriptions of the earliest iv injections of various substances by individuals who actually witnessed the experiments in 1656 are presented. Of particular interest is an apparently overlooked account of an experiment in which opium was administered intravenously to a dog many years before 1674 as related by the physician and anatomist Thomas Willis. He does not identify the precise date nor the experimenters. However, at the time of this event Willis would have been at Oxford. There he was a very close professional associate of Christopher Wren who originated the practice of iv injection. These eyewitness accounts are worthy of note because the articles usually cited to establish Wren as the first individual to administer a drug intravenously were not written by anyone who actually observed the experiments.

Anesthesia, Intravenous↗
PubMed1989

Cancer risk in population examined with diagnostic doses of 131I.

Previously, we conducted a study of 35,074 patients receiving diagnostic doses of 131I for suspected thyroid disorders between 1951 and 1969. We reported that, between 1958 and 1984, the incidence of thyroid cancers in these patients was insignificantly greater than the incidence expected in the general population. This increase was attributed to the underlying condition that prompted the examination and not to the administration of 131I. The purpose of the present study was to analyze the total cancer risk in the same cohort of patients examined with diagnostic doses of 131I. To further evaluate the underlying risk of disease in these patients, we compared the incidence of all cancers with that expected in the general population. The average radiation dose was approximately 500 mGy to the thyroid and less than 10 mGy to other organs. In the 35,074 patients, 3,746 cancers occurred following the first 5 years after examination, and the resulting standardized incidence rate (SIR) was 1.01 (95% confidence interval = 0.98-1.04). SIRs were significantly increased for endocrine tumors other than thyroid cancer (1.93) and for lymphomas (1.24), leukemias (1.34), and nervous system tumors (1.19). The risk of leukemia was similar for chronic lymphocytic leukemia (CLL) (SIR = 1.30) and non-CLL (SIR = 1.34). SIR was significantly decreased for cancers of the female genital organs (0.86). The risk for cancer of all sites and types combined was highest 5-9 years after examination (SIR = 1.07) and did not differ from unity thereafter. With greater than or equal to 10 years of follow-up, risk was not statistically associated with the dose of 131I. Overall, the data exclude cancer risk increments greater than 5% (SIR = 1.05) with 95% confidence. The significant increase in the risk of non-CLL, a prominent radiogenic malignancy, however, warrants special attention. We are continuing our study to determine the possible factors involved in the significant increase in the risk of leukemia.

Adult↗
PubMed1988

Thyroid cancer after diagnostic doses of iodine-131: a retrospective cohort study.

The incidence of thyroid cancer was evaluated in 35,074 patients examined for suspected thyroid disorders between 1951 and 1969 with an average of 1.92 megabecquerel [(MBq) 52 microCi] of 131I. The radiation dose to the thyroid gland was, on the average, approximately 0.5 Gy. The mean age at the time of examination was 44 years; 5% were under age 20. Patients were followed for an average of 20 years. Record linkage with the Swedish Cancer Register identified 50 thyroid cancers occurring 5 years or more after the initial 131I examination, in contrast to 39.4 expected based on general population rates [standardized incidence ratio (SIR) = 1.27, 95% confidence interval = 0.94-1.67]. Risk was highest among males (SIR = 2.70, n = 10), patients followed 5-9 years (SIR = 2.22, n = 23), and patients receiving more than 74 microCi or 2.74 MBq of 131I (SIR = 2.04, n = 17). However, these observations were confounded by the fact that patients examined for a suspected thyroid tumor received the highest 131I exposures and were at highest overall risk (SIR = 2.77, n = 34). Patients given 131I for reasons other than a suspected tumor were not at increased risk (SIR = 0.62, n = 16). Patients anticipated to be at highest risk, i.e., women (SIR = 1.12, n = 40) and those observed for 10 years or more (SIR = 0.93, n = 27), showed no evidence of a dose response. Overall, these data provide little proof that 131I is carcinogenic in humans and support the notion that the carcinogenic potential of internal 131I beta particles might be as low as four times less than external x rays or gamma rays.

Adolescent↗
PubMed1986

Effect of isoflurane on bronchomotor tone in man.

Twenty patients were anaesthetized with thiopentone, the trachea intubated and the lungs ventilated with 70% nitrous oxide and oxygen. Normocapnia was maintained and, following control measurements of the specific conductance of the lower airways (s.Glaw), either 1.7% isoflurane or 1.3% halothane was added to the inspired gas mixture, 10 patients receiving each drug. s.Glaw was measured repeatedly during the next 30 min. There was a tendency for s.Glaw to increase--indicating a reduction in bronchomotor tone--during the administration of isoflurane, the effect approaching statistical significance. The administration of halothane was associated with a significant increase in s.Glaw. There was a statistically significant increase in the expiratory reserve volume, and a decrease in mean respiratory resistance over the tidal range in both groups. These results indicate that isoflurane does not cause an increase in bronchomotor tone, and may have a tendency to decrease it. This suggests that the previously reported increase of respiratory resistance during isoflurane anaesthesia resulted from a reduction in lung volume, rather than a change in bronchomotor tone.

Adolescent↗
PubMed1986

The influence of nitrous oxide on oxyhaemoglobin dissociation and measurement of oxygen tension.

There are conflicting reports of the effect of nitrous oxide on the oxyhaemoglobin dissociation curve. We have therefore determined P50 of haemoglobin in the presence of either nitrous oxide or nitrogen and studied the upper portion of the curve in greater detail. No significant differences in the oxyhaemoglobin dissociation curve were observed when nitrous oxide was substituted for nitrogen. The oxygen tensions measured in gas mixtures were not significantly different when determined simultaneously with a polarographic oxygen electrode and the mass spectrometer when nitrous oxide was used instead of nitrogen.

Humans↗
PubMed1985

Samuel Latham Mitchill (1764-1831). A neglected American pioneer of anesthesia.

In 1795, Samuel Latham Mitchill, MD, of New York City published a theory of contagion. He proposed that the cause of plaguelike disease was exposure to "gaseous oxide of azote" (nitrous oxide). During the course of his exposition of this theory, Mitchill presented a clear and vivid description of the effects of nitrous oxide inhalation and the resulting anesthetic state. This earliest description of nitrous oxide narcosis appears to have been overlooked. It antedates that of Humphry Davy by five years. Samuel Latham Mitchill should be accorded an important position among the pioneers of anesthesia because of this description and also because his interest in nitrous oxide was the direct stimulus for Humphry Davy's investigations, ultimately leading to introduction of anesthesia into clinical practice.

Anesthesiology↗
PubMed1984

Changes in lung volume and (PAO2-PaO2) during anaesthesia.

The theory, that the decrease in lung volume which occurs after induction of general anaesthesia is the cause of the higher (PAO2-PaO2) during anaesthesia, was examined in 18 patients. Lung volume was increased during anaesthesia by changing the posture of the patient to 30 degrees head-up, but there was no improvement in (PAO2-PaO2). There were no correlations between change in (PAO2-PaO2) and in cardiac output between different postures. It is concluded that gas exchange is independent of change in lung volume during anaesthesia, at least over the range examined. It remains possible that restoration of lung volume to pre-anaesthetic values may not restore regional distribution of ventilation to pre-anaesthetic values.

Adolescent↗