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Biomedical subjects

L McKay

Publications and source records attributed to L McKay.

At least 19 recordsLinked to original sources
PubMed2003

Natural attenuation of trichloroethylene in fractured shale bedrock.

This paper describes one of the first well-documented field examples of natural attenuation of trichloroethylene (TCE) in groundwater in a fractured shale bedrock. The study was carried out adjacent to a former waste burial site in Waste Area Grouping 5 (WAG5) on the Oak Ridge Reservation, Oak Ridge, TN. A contaminant plume containing TCE and its daughter products were detected downgradient from the buried waste pits, with most of the contamination occurring in the upper 6 m of the bedrock. The monitoring well array consists of a 35-m-long transect of multilevel sampling wells, situated along a line between the waste pits and a seep which discharges into a small stream. Concentrations of volatile organic carbons (VOCs) were highest in the waste trenches and decreased with distance downgradient towards the seep. Sampling wells indicated the presence of overlapping plumes of TCE, cis-dichloroethylene (cDCE), vinyl chloride (VC), ethylene, ethane, and methane, with the daughter products extending further downgradient than the parent (TCE). This type of distribution suggests anaerobic biodegradation. Measurements of redox potential at the site indicated that iron-reduction, sulfate reduction, and potentially methanogensis were occurring and are conducive to dechlorination of TCE. Bacteria enrichment of groundwater samples revealed the presence of methanotrophs, methanogens, iron-reducing bacteria and sulfate-reducing bacteria, all of which have previously been implicated in anaerobic biodegradation of TCE. 16S rDNA sequence from DNA extracted from two wells were similar to sequences of organisms previously implicated in the anaerobic biodegradation of chlorinated solvents. The combined data strongly suggest that anaerobic biodegradation of the highly chlorinated compounds is occurring. Aerobic biodegradation may also be occurring in oxygenated zones, including near a seep where groundwater exits the site, or in the upper bedrock during seasonal fluctuations in water table elevation and oxygen levels.

Biodegradation, Environmental↗
PubMed2001

The effects of cervical application of inhibitors of inducible nitric oxide synthase, cyclooxygenase-1, and cyclooxygenase-2 on delivery in rats.

OBJECTIVE: To investigate the effect of cervical application of nonselective and selective inhibitors of nitric oxide synthases--N-nitro-L-arginine methyl ester, L-N-iminoethyl-lysine, and aminoguanidine--as well as inhibitors of cyclooxygenases--indomethacin, and nimesulide--on timing of delivery and fetal death and disease in pregnant rats. STUDY DESIGN: In a series of experimental protocols, timed-pregnant Sprague-Dawley rats (length of pregnancy, 22 days) were randomly allocated to daily cervical applications of (1) 0.04 mg (n = 6), 0.4 mg (n = 6), 4 mg (n = 6), or 40 mg (n = 6) L-N-iminoethyl-lysine or vehicle (n = 12) on days 19 to 22 of pregnancy; (2) 50 mg aminoguanidine (n = 6), 150 mg aminoguanidine (n = 6), or vehicle (n = 10) on days 19 to 22 of pregnancy; (3) 3 mg indomethacin (n = 6) or vehicle (n = 6) on days 19 to 22 of pregnancy; (4) 12.5 mg/kg nimesulide (n = 8), 25 mg/kg nimesulide (n = 8), 50 mg/kg nimesulide (n = 12), or vehicle (n = 12) on days 19 to 22 of pregnancy and 50 mg/kg nimesulide (n = 23) or vehicle (n = 23) on days 14 to 22 of pregnancy; (5) 50 mg/kg nimesulide (n = 10), 50 mg aminoguanidine plus 50 mg/kg nimesulide (n = 10), 50 mg aminoguanidine (n = 10), or vehicle (n = 10) on days 14 to 22 of pregnancy. The following variables were evaluated: proportion of animals that were delivered on day 23, time to delivery of the first pup (midnight on day 22 was considered to be 0 hour), number of stillborn pups, and average pup weight of each litter. RESULTS: Unlike L-N-iminoethyl-lysine, aminoguanidine, and indomethacin, 50 mg/kg nimesulide applied on the cervix daily for 8 days significantly increased the proportion of animals that were delivered on day 23 (18 of 23 versus 7 of 23; P =.003) and the time to delivery of the first pup by a mean of 10.8 hours (P <.001). Shorter treatment with nimesulide for 4 days increased only the time to delivery of the first pup at the 25-mg/kg dosage (P =.008). Simultaneous application of aminoguanidine and nimesulide significantly (P =.008) prolonged pregnancy to a degree similar to nimesulide alone. The experiment with N-nitro-L-arginine methyl ester was aborted because of severe maternal side effects. Unlike pups in the L-N-iminoethyl-lysine, aminoguanidine, and nimesulide groups, significantly more pups in the indomethacin group died in utero compared with the control group (36.1% versus 3.1%; P <.001), and the surviving pups had lower birth weights (P <.001). CONCLUSIONS: In an animal model, nimesulide was effective in delaying the onset of labor, was well tolerated during pregnancy, and affected cervical ripening directly independent of progesterone withdrawal. Conversely, cervical application of nitric oxide synthase and nonselective cyclooxygenase inhibitors do not extend the duration of pregnancy in the dosages studied, and some are associated with significant adverse effects in the mothers and fetuses.

Administration, Topical↗
PubMed2001

Therapeutic plasma exchange.

The improvement in design and biocompatibility of continuous renal replacement therapy equipment has made it possible to perform therapeutic plasma exchange (TPE) in the intensive care unit. The purpose of this article is to outline the general principles of apheresis, including a historical perspective, current indications, and complications. Replacement fluid, membrane filtration, anticoagulation, and vascular access will be presented. A summary of the nursing care associated with TPE, potential complications, and methods to reduce the risk of their occurrence are summarized.

Anticoagulants↗
PubMed1997

Home birth in New Zealand 1973-93: incidence and mortality.

AIMS: To determine for the period 1973-93, national and regional (1991 and 1992 only) incidence of home birth in New Zealand, with home birth defined as home being the intended place of birth at the onset of labour, to calculate perinatal and maternal mortality rates for home birth, and to categorise the cause of perinatal death. METHODS: Data sheets for 9776 planned home births were analysed. These had been collected by the Home Birth Associations of New Zealand/Aotearoa. National perinatal data and data from National Women's Hospital, Auckland were used for comparison. Trend analysis was performed by Poisson regression allowing for overdispersion. RESULTS: Planned home birth made up 2% of the total births in 1993, up from 0.04% in 1973. The home birth perinatal mortality rate for this period was 2.97 per 1000 total births, with no change over time. This was not significantly different from the rate for a selected low risk group at National Women's Hospital. Lethal anomalies caused 31% of the perinatal deaths. There was one maternal death (maternal mortality rate: 1.02 per 10,000 total births). There were significant differences in the rate of home birth in separate area health board regions for 1991 and 1992. CONCLUSION: Home birth was a safe and increasingly popular: though minor, option for New Zealand women from 1973-93.

Cause of Death↗
PubMed1995

Time trend in pancreatic cancer incidence in Connecticut, 1935-1990.

A total of 13,246 incident pancreatic cancer cases, reported to the Connecticut Tumor Registry between 1935 and 1990, were included in our study. Results indicate that the overall age-adjusted incidence rate of pancreatic cancer increased between 1935 and 1964 in males, and leveled off thereafter. Since 1975, the incidence rate has in fact been decreasing, from 12.04/100,000 in 1975-79 to 10.44/100,000 in 1985-90. In females, the overall age-adjusted incidence rate also increased between 1935 and 1974. Since then, however, it has remained relatively stable. Age-specific incidence rates also show no signs of an increase in rate from any age group, or from either sex for recent birth cohorts. There is also no clear increase in the incidence of pancreatic cancer in any of the ethnic/gender categories since the early 1970s. Age-period-cohort modeling shows that the increasing birth cohort trend peaked among those born around 1920-1925 and, for recent birth cohort, a slightly decreasing trend was observed in both males and females. Our study reveals no signs of an increase in the immediate future in pancreatic cancer incidence rate in any of the sex, ethnic and age groups in Connecticut.

Adult↗
PubMed1995

Differential dynamics of receptor down-regulation and tyrosine aminotransferase induction following glucocorticoid treatment.

Autoregulation of glucocorticoid receptor (GR) concentration in vivo may be an important determinant of steroid sensitivity. The dynamics of GR regulation were assessed and compared to regulation of tyrosine aminotransferase (TAT) expression in liver tissue taken from rats treated with a single 50 mg/kg i.v. dose of methylprednisolone. Plasma methylprednisolone concentrations were determined by HPLC analysis. Receptor and TAT message levels were determined by quantitative Northern hybridization. Methylprednisolone plasma kinetics showed a half-life of 0.6 h. Receptor occupancy occurred rapidly and cytosolic GR reappeared over 2-12 h. TAT activity rose between 2 and 6 h and then dissipated. Reduction in receptor mRNA levels occurred very rapidly, being detectable by 30 min following steroid administration. A down-regulated steady-state in GR message expression was reached by 2 h post-injection, and was maintained throughout the 18 h examined in this study. Comparison of methylprednisolone kinetics demonstrated that down-regulation was maintained long after drug was eliminated. In contrast, TAT message induction occurred with a sharp peak; maximal induction occurred between 5-6 h and return to baseline at approx. 8-10 h post-induction. This study shows that unlike TAT induction, GR message repression in vivo does not require continual presence of hormone.

Adrenalectomy↗
PubMed1995

Health concerns of adolescent girls.

An anonymous self-report questionnaire designed to assess adolescent girls' health concerns was administered to 1,416 female students in grades 7-10 from 38 schools in northwestern Ontario. Results indicated that the future and items of appearance were of the highest level of concern in the sample. Factor analysis of the 27 concern items produced grouping of concerns into four factors: risk-taking behavior, appearance, health promotion/future orientation, and psychological functioning. Comparison of the four factors across grades revealed that concern about risk-taking behavior and psychological functioning did not change; concern about health promotion/future orientation issues decreased as the grade increased; and concern about appearance increased as the grade increased. It is anticipated that the grouping of concerns and differences by grade revealed in this study will assist in designing pertinent health programs to interest and motivate the teenage female population.

Adolescent↗
PubMed1994

Rapid increase in desflurane concentration is associated with greater transient cardiovascular stimulation than with rapid increase in isoflurane concentration in humans.

BACKGROUND: Increases in desflurane and isoflurane concentrations can transiently increase arterial blood pressure or heart rate or both during induction of anesthesia. The current study tested the hypothesis that a rapid increase of desflurane concentration in humans increases sympathetic activity and hormonal variables and heart rate and arterial blood pressure more than does an equivalent increase in isoflurane concentration. METHODS: Twelve healthy male volunteers were assigned randomly to receive desflurane and on a separate occasion isoflurane. After induction of anesthesia with propofol 2 mg/kg, anesthesia was maintained at 0.55 MAC (desflurane, 4.0%; isoflurane 0.71% end-tidal) for 32 min. Mechanical ventilation maintained normocapnia throughout anesthesia. Mean arterial blood pressure and heart rate were recorded continuously, and arterial blood was sampled for plasma catecholamine and vasopressin (AVP) concentrations, and plasma renin activity. Anesthetic concentration was increased rapidly to 1.66 MAC (desflurane, 12.0%; isoflurane 2.12% end-tidal), and maintained at this concentration for 32 min, and then rapidly decreased to and maintained at 0.55 MAC for an additional 32 min. RESULTS: Neither anesthetic produced sympathetic or cardiovascular stimulation during their initial rapid wash-in to 0.55 MAC. The rapid increase to 1.66 MAC increased mean arterial blood pressure, heart rate, and plasma epinephrine and norepinephrine concentrations, and plasma renin activity with both desflurane and isoflurane, the former usually producing a response of greater magnitude than the latter. Plasma AVP concentration increased with desflurane only. Increased mean arterial blood pressure returned to control in 4 min. Heart rate decreased 50% of the difference between its peak and the value at 32 min at 1.66 MAC in 2 min with desflurane and in 4 min with isoflurane but did not return to the value at 0.55 MAC with either anesthetic. With desflurane, plasma epinephrine and AVP concentrations decreased quickly from their peak values, remaining elevated for 8 min. Decrease of concentrations of desflurane and isoflurane from 1.66 MAC to 0.55 MAC rapidly decreased heart rate and increased mean arterial blood pressure with both anesthetics. Thirty-two minutes after return to 0.55 MAC, with both anesthetics, only heart rate remained increased relative to the values at 32 min of the initial period of 0.55 MAC anesthesia. CONCLUSIONS: In healthy male volunteers, rapid increases of desflurane or isoflurane from 0.55 to 1.66 MAC increase sympathetic and renin-angiotensin system activity, and cause transient increases in arterial blood pressure and heart rate. Desflurane causes significantly greater increases than isoflurane, and also causes a transient increase in plasma AVP concentration. The temporal relationships suggest that the increased sympathetic activity increases mean arterial blood pressure and heart rate, with mean arterial blood pressure also increased by increased plasma AVP concentration, whereas the delayed, increased plasma renin activity is likely a response to the ensuing hypotension, or earlier inhibition by AVP, or both.

Anesthesia, General↗
PubMed1994

Rapid 1% increases of end-tidal desflurane concentration to greater than 5% transiently increase heart rate and blood pressure in humans.

BACKGROUND: Large (0.5-1.0 MAC), rapid increases of desflurane to concentrations greater than 5% can transiently increase heart rate, mean arterial blood pressure (MAP), sympathetic nerve activity, and plasma epinephrine concentration. We tested the hypothesis that small (1% = 0.14 MAC), rapid increases of desflurane concentration to greater than 5% do not increase heart rate, blood pressure, and plasma catecholamine concentrations. METHODS: Anesthesia was induced with intravenous propofol, 2 mg/kg, in 13 healthy male volunteers, 19-33 yr of age, and ventilation was controlled to maintain normocapnia. We gave 4% end-tidal desflurane in oxygen for 32 min and then imposed successive 1% increases in end-tidal desflurane concentration, each new concentration maintained for 4 min, to a final concentration of 12%. We measured heart rate, MAP and plasma catecholamine concentrations in the awake state, after 4 min at each 1% step, and at times of peak increase of MAP (> or = 10% change). RESULTS: Increases in heart rate and blood pressure of more than 10% occurred with 1% step-increases in only 1 volunteer at 5% desflurane but in 7-10 (MAP) and 8-12 (heart rate) of the 13 volunteers at higher desflurane concentrations. The 1% increases in desflurane concentration to greater than 5% also transiently increased plasma epinephrine concentrations but not vasopressin concentration or plasma renin activity in those volunteers in whom MAP increased. CONCLUSIONS: Small (1%) increases in desflurane concentration to and greater than 6% can transiently increase heart rate, mean arterial pressure, and plasma epinephrine concentration. These data and those from a previous study indicate that these increases occur with a lesser frequency and magnitude than those associated with a single, rapid step from 4% to 12% end-tidal desflurane.

Adult↗
PubMed1993

Diastereomeric phosphonate ester adducts of chymotrypsin: 31P-NMR measurements.

Generation of diastereomeric phosphonate ester adducts of chymotrypsin was evidenced for the first time by 31P NMR and spectrophotometric kinetic measurements. 31P NMR signals were recorded for 4-nitrophenyl 2-propyl methylphosphonate (IMN) at 32.2 ppm and for its hydrolysis product at 26.3 ppm downfield from phosphoric acid. The inhibition of alpha-chymotrypsin at pH > 8.0 by the faster reacting enantiomer of IMN or 2-propyl methylphosphonochloridate (IMCL), or other phosphonate ester analogs of these compounds, all caused a approximately 6.0 ppm downfield shift of the 31P signal to the 39-40 ppm region. IMN, when applied below the stoichiometric amount of chymotrypsin, under the same conditions, generated two signals, at 39.0 and at 37.4 ppm. Scans accumulated in hourly intervals showed the decomposition of both diastereomers, with approximate half-lives of 12 h at pH 8.0 and 22 degrees C, into a species with a resonance at 35.5 ppm. The most likely reaction to account for the appearance of this new peak is the enzymic dealkylation of the isopropyl group from the covalently bound phosphonate ester. We base this conclusion mostly on the similarity of the upfield shift to the hydrolysis of phosphonate esters. Contrary to experience with phosphate ester adducts of serine proteases, no signal was detected higher than 25.0 ppm downfield from phosphoric acid for several phosphonate ester adducts of chymotrypsin and in no case did the resonance for the adduct shift further downfield in the course of the experiments.

Chymotrypsin↗
PubMed1992

A reversal in the long-term increase in deaths attributable to malignant melanoma.

For a few years in the 1980s, United States mortality rates suggested a plateau in the long-term increase for malignant melanoma. However, temporary plateaus in the increase of the age-adjusted rate by year of death have occurred in previous decades, only to be followed by a continued upward increase, with a long-term rise of about 2% per year. To determine whether a cessation in the long-term increase might be in progress, death rates were analyzed by year of birth, age at death, and year of death: (1) the long-term patterns of change are best described by birth cohort rather than by time period of death, indicating that analyses by a year of birth are key to a better understanding of the long-term trends; (2) in both men and women, evidence for a change in slope begins among those born in the early 1930s; (3) the decline in the rates begins among women born since the early 1930s and among men born since the early 1950s: the slope for men is -0.2661 (95% confidence limits [CL] = -0.380 to -0.152), and, for women, the slope is -0.02354 (95% CL = -0.041 to -0.005); (4) long-term Connecticut and US mortality trends were similar in pattern and direction, and long-term Connecticut incidence rates showed a persistent increase through the 1955 to 1965 birth cohorts. These analyses suggest a persistent cessation in the long-term increase and a downward trend in death rates from this cancer.

Adolescent↗
PubMed1992

Melanotropin as a potential regulator of pigment pattern formation in embryonic skin.

Frozen tissue sections of developing axolotl embryos were labeled by indirect immunofluorescence with anti-alpha-MSH. Anti-MSH immunoreactivity is first detectable in embryos when neural crest cells are migrating from the neural tube. Antibody labeling is visible around the lateral and ventral edges of the neural tube and in the embryonic ectoderm. As development progresses, the amount of labeling increases greatly, particularly in developing ectoderm. Western blots of soluble proteins extracted from various developmental stages of axolotl embryo ectoderm reveal that MSH activity is associated directly with several high molecular weight components that may be part of the embryonic extracellular matrix. Thus, we suggest that melanotropin activity is present in embryonic axolotl skin, is associated with the extracellular matrix, and is thereby in a position to play a supportive and/or directive role in the establishment of embryonic pigment patterns.

Ambystoma↗
PubMed1988

Percutaneous balloon mitral valvuloplasty in a pregnant woman with mitral stenosis.

A 39-year-old woman with symptomatic mitral stenosis underwent percutaneous mitral valvuloplasty at the end of her first trimester of pregnancy. Balloon dilatation utilizing a double 18-20 mm balloon technique resulted in improvement in mean mitral gradient (16 to 7 mmHg) and in calculated mitral valve area (1.4 to 2.4 cm2), without significant complications and with an estimated radiation exposure to the fetus of less than 0.2 rads. The procedure resulted in disappearance of symptoms of congestive heart failure and allowed for discontinuation of diuretics. The subsequent course of gestation was uncomplicated and a normal baby boy was delivered in the 36th wk. We conclude that percutaneous mitral valvuloplasty may produce successful palliation of symptoms in patients with mitral stenosis during pregnancy.

Adult↗