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Biomedical subjects

L D Nelson

Publications and source records attributed to L D Nelson.

At least 19 recordsLinked to original sources
PubMed1995

Fundulus heteroclitus vitellogenin: the deduced primary structure of a piscine precursor to noncrystalline, liquid-phase yolk protein.

We have cloned and sequenced a cDNA encoding a vitellogenin (Vtg) from the mummichog, Fundulus heteroclitus, an estuarine teleost. We constructed a liver cDNA library against RNA from estrogen-treated male mummichogs. Five overlapping cDNA clones totalling 5,197 bp were isolated through a combination of degenerate oligonucleotide probing of the library and PCR. The cDNA sequence contains a 5,112 bp open reading frame. The predicted primary structure of the deduced 1,704-amino-acid protein is 30-40% identical to other documented chordate Vtgs, establishing this Vtg as a member of the ancient Vtg gene family. Of the previously reported chordate Vtg sequences (Xenopus laevis, Gallus domesticus, Ichthyomyzon unicuspis, and Acipenser transmontanus), all four act as precursor proteins to a yolk which is eventually rendered insoluble under physiological conditions, either as crystalline platelets or as noncrystalline granules. The yolk of F. heteroclitus, on the other hand, remains in a soluble state throughout oocyte growth. The putative F. heteroclitus Vtg contains a polyserine region with a relative serine composition that is 10-20% higher than that observed for the other Vtgs. The trinucleotide repeats encoding the characteristic polyserine tracts of the phosvitin region follow a previously reported trend: TCX codons on the 5' end and AGY codons toward the 3' end. Whether the difference in Vtg primary structure between F. heteroclitus and that of other chordates is responsible for the differences in yolk structure remains to be elucidated. As the first complete teleost Vtg to be reported, these data will aid in designing nucleotide and immunological probes for detecting Vtg as a reproductive status indicator in F. heteroclitus and other piscine species.

Amino Acid Sequence↗
PubMed1995

Mutations in exon 17B of cartilage oligomeric matrix protein (COMP) cause pseudoachondroplasia.

Pseudoachondroplasia (PSACH) is a well characterized dwarfing condition mapping to chromosome 19p12-13.1. Cartilage oligomeric matrix protein (COMP), a cartilage specific protein, maps to the same location within a contig that spans the PSACH locus. Using single strand conformation polymorphism (SSCP) analysis and nucleotide sequencing we have identified COMP mutations in eight familial and isolated PSACH cases. All mutations involve either a single base-pair change or a three base-pair deletion in exon 17B. Six mutations delete or change a well conserved aspartic acid residue within the calcium-binding type 3 repeats. These results demonstrate that mutations in the COMP gene cause pseudochondroplasia.

Achondroplasia↗
PubMed1995

Survival in patients with severe adult respiratory distress syndrome treated with high-level positive end-expiratory pressure.

OBJECTIVE: To assess the mortality rate and complications in a population of surgical patients with severe adult respiratory distress syndrome (ARDS) treated with positive end-expiratory pressure (PEEP) of > 15 cm H2O in an attempt to reduce intrapulmonary shunt to approximately 0.20 and reduce FIO2 to < 0.50. DESIGN: Retrospective review of patients treated by a standardized ventilatory support protocol at the time of their illness. SETTING: A 24-bed surgical intensive care unit in a university medical center. PATIENTS: All patients admitted to the surgical intensive care unit during a 34-month period who met the criteria for severe ARDS (Pao2 of < or = 70 torr [< or = 9.3 kPa] on an FIO2 of > or = 0.50, diffuse interstitial and/or alveolar infiltrates on chest radiograph, decreased lung compliance, no evidence of congestive heart failure, and a likely predisposing etiology) were evaluated. Patients treated with PEEP of > 15 cm H2O were selected for this review. INTERVENTIONS: Patients were treated by a protocol to achieve oxygenation end points, which consisted of maintaining arterial oxyhemoglobin saturation (as determined by pulse oximetry of > or = 0.92), while reducing FIO2 to < 0.50 and decreasing intrapulmonary shunt fraction to < or = 0.20 by adding PEEP. With the exception of patients with suspected intracranial hypertension related to closed-head injury, low-rate intermittent mandatory ventilation was the primary mode of ventilation. Pressure-support ventilation was added, when needed, to improve patient comfort, enhance spontaneous tidal volume, or improve CO2 excretion. MEASUREMENTS AND MAIN RESULTS: Eighty-six patients with severe ARDS were treated with a PEEP of > 15 cm H2O. Nineteen of these patients died early of severe closed-head injury or massive uncontrollable hemorrhage and were excluded from the evaluation. The remaining 67 patients had a mean Lung Injury Score of 3.3 during their treatment with high PEEP. Twenty (30%) of 67 patients died. Eight of the deaths occurred after decrease of ventilatory support and with acceptable blood gases. The other 12 patients who died had continued oxygenation deficits and received increased levels of ventilatory support at the time of death. Twenty-six (39%) of 67 patients had radiographic manifestations of barotrauma (pneumothorax, subcutaneous emphysema, etc.) related to their primary injuries or to complications related to central venous catheter placement. Seven (17%) of 41 patients developed clinical or radiographic signs of barotrauma while receiving high-level PEEP. The hemodynamic effects of increased airway pressure were managed with fluids and inotropic agents, when necessary, and did not limit the application of PEEP to reach the defined end point of treatment. CONCLUSIONS: This subset of patients with severe ARDS treated with high-level PEEP had a mortality rate lower than those rates previously reported by other researchers using more conventional ventilatory support and resuscitation techniques. FIO2 may be significantly reduced and PaO2 may be maintained at acceptable values by decreasing intrapulmonary shunt fraction using high-level PEEP.

Adult↗
PubMed1992

High-level positive end-expiratory pressure management in trauma-associated adult respiratory distress syndrome.

This study evaluated the effect of high-level positive end-expiratory pressure (PEEP) on mortality, barotrauma, intrapulmonary shunt (Qsp/Qt), and oxygen delivery (DO2) in posttraumatic adult respiratory distress syndrome (ARDS). All hypoxemic trauma patients admitted to the surgical intensive care unit (SICU) in 1989-1990 who received PEEP greater than 15 cm H2O were included. The PEEP was titrated to achieve an intrapulmonary shunt (Qsp/Qt) of approximately 0.20, and FIO2 was weaned to less than 0.50. Hemodynamic and pulmonary variables at four distinct intervals were recorded. Fifty-nine patients received PEEP greater than 15 cm H2O. Of these, 19 patients died of severe head injury or uncontrollable hemorrhage (16 within 48 hours). Forty (29 male, 11 female) were evaluated in detail. The PEEP levels ranged from 18-50 cm H2O with a mean of 27. PaO2/FIO2 ratios and Qsp/Qt improved as PEEP therapy was titrated. Cardiac index and oxygen delivery were maintained or improved throughout PEEP therapy by transfusion and fluid resuscitation, with a mean maximum positive fluid balance of 21.1 L and an average of 51 units of blood and blood products transfused per patients during their SICU stay. Twenty-nine (73%) had evidence of barotrauma, the majority being pneumothoraces clearly related to the initial trauma. Only three (7.5%) had evidence of barotrauma not related to trauma or line insertion. Eight of 40 patients (20%) died. Mean ISS and RTS for the entire group were 32 and 5.88, respectively. We conclude that titration of PEEP to achieve a Qsp/Qt of approximately 0.20 is an attainable goal. This was accomplished with minimal hemodynamic effects or barotrauma and a low mortality rate.

Adolescent↗
PubMed1992

Antibody response of calves to immunoaffinity-purified bovine respiratory syncytial virus VP70 after vaccination and challenge exposure.

Immunoaffinity-purified bovine respiratory syncytial virus (BRSV) fusion (F) protein elicited anti-BRSV-specific antibody responses in BRSV-seronegative calves. After primary vaccination, all calves seroconverted to BRSV as determined by the virus neutralization (VN) test and developed anti-F protein antibodies detectable by protein immunoblot analyses. Subsequent vaccinations induced greater than twofold increase in VN titer in 3 of 9 (33%) calves, and 1 calf became VN-negative, but still had nonneutralizing antibody detectable by protein immunoblot analysis. This calf remained seronegative after challenge exposure. Two groups of calves were vaccinated IM with immunoaffinity-purified BRSV F protein. Each dose was 2 ml containing 20 micrograms of purified F protein. Freund's adjuvants were used for all vaccinations, with Freund's complete adjuvant used for the primary vaccination and Freund's incomplete adjuvant for subsequent vaccinations. The vaccine was administered to both groups at weeks 0 and 3; the first group received a third vaccination at weeks 21. Group-1 and -2 vaccinated calves and non-vaccinated contact controls were intranasally aerosol challenge-exposed with low cell culture-passage BRSV on weeks 22 and 9, respectively. Eight of 9 vaccinated calves did not develop a humoral anamnestic response following challenge exposure, as demonstrated by VN test and protein immunoblot analyses. Calf 14 from group 1 which had a 1:2 VN antibody titer prior to vaccination, was the only calf that developed an anamnestic response.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

2-Hydroxydesipramine and desipramine plasma levels and electrocardiographic effects in depressed younger adults.

Desipramine was given to 34 outpatients aged 20 to 51 years who had primary major depressive disorder but who were otherwise in good health. Daily dosage at bedtime was constant for the final 3 weeks of the 5-week study (mean, [SD] 169.1 [46.1] mg). Electrocardiograms done predrug and after 5 weeks were read by a cardiologist blind to the order in which they were performed. Plasma samples drawn 14 hours after the final study dose were assayed by high performance liquid chromatography; mean (SD) levels were 140.2 (140.0) ng/ml for desipramine and 56.5 (29.4) ng/ml for 2-hydroxydesipramine (2-OH-DMI). Heart rate and PR, QRS and QTc intervals were significantly greater at the end of the study than at baseline, while QT intervals were significantly less. Changes in heart rate and PR, QT and QTc intervals were significantly negatively correlated with the value of the respective cardiac parameters at baseline. Changes in PR interval were significantly positively correlated with log desipramine, log 2-OH-DMI and log (desipramine + 2-OH-DMI). Stepwise multiple regression analyses showed that, for PR interval, each of the three plasma level variables showed a significant ability to improve R2 over that obtained from baseline PR alone. These findings suggest that both 2-OH-DMI and desipramine plasma levels predict a prolongation of intracardiac conduction in younger adults and that monitoring both levels may be useful in the clinical management of certain younger adult patients.

Adult↗
PubMed1990

Evaluation of APACHE II for cost containment and quality assurance.

APACHE II (an acronym formed from acute physiology score and chronic health evaluation) has been proposed to limit intensive care unit (ICU) admissions ('cost containment') and to judge outcome ('quality assurance') of surgical patients. To judge its performance, a 6-month study of 372 surgical ICU patients was performed. When patients were divided by mean duration of stay, mortality rates rose from 1% (short stay) to 19% (long stay) (p less than 0.001) for patients with APACHE II scores less than 10, but decreased from 94% (short stay) to 60% (long stay) (p less than 0.01) for patients with APACHE II scores more than 24. Exclusion of patients by high or low APACHE scores would 'save' 6% of ICU days but risk increasing morbidity, hospital costs, and deaths. Grouped APACHE II scores did not correlate with total hospital charges (r = 0.05, p = 0.89) or ICU days used (r = 0.42, p = 0.17). Grouping by APACHE II score and duration of ICU stay showed neither symmetry nor uniformity of mortality rates. Surgical patients would not be well served by APACHE II for quality assurance or cost containment.

Adult↗
PubMed1990

Use of recombinant human erythropoietin (r-HuEPO) in a Jehovah's Witness refusing transfusion of blood products: case report.

Recombinant human erythropoietin (r-HuEPO) administration to a Jehovah's witness refusing blood transfusions increased her nadir packed cell volume from 13% to 37% and reticulocyte count from 2% to 17.7%. R-HuEPO may provide an alternative safe and effective therapy in life-threatening anemia when blood transfusions are unacceptable to the patient.

Accidents, Traffic↗
PubMed1989

Errors in estimating energy expenditure in critically ill surgical patients.

Thirty-one critically ill surgical patients were receiving central parenteral nutrition. All were intubated, and 29 were receiving mechanical ventilatory support. Nutritional and metabolic data were recorded at the time of indirect calorimetry. Measured energy expenditure (MEE) was compared with predictions of basal energy expenditure (BEE) and calculated energy expenditure, defined as the product of BEE and a stress factor estimated by the nutrition support service to account for severity of illness and activity. The MEE was significantly greater than the BEE and significantly less than the calculated energy expenditure. The estimated stress factor was significantly greater than the actual MEE/BEE ratio, and the correlation between these values was poor. Clinical assessment may overestimate energy expenditure in critically ill patients because of the apparent degree of illness used to determine the stress factor. Bedside indirect calorimetry may be useful to assess more accurately energy expenditure and optimize nutritional support.

Adolescent↗
PubMed1989

Physiologic effects of steep positioning in the surgical intensive care unit.

Ten hemodynamically stable patients requiring mechanical ventilation for radiographically symmetric acute lung disease were studied during steep lateral positioning and continuous rotation in a Roto Rest kinetic treatment bed. There were no significant hemodynamic or ventilatory differences among the four positions (supine, right side down, left side down, and rotating). In four patients, arterial oxygen pressure (PaO2) decreased 16% to 49% in the lateral position when compared with the supine position. Continuous rotation restored the PaO2 toward the supine value in each patient. In six patients, PaO2 increased 11% to 35% during lateral positioning. In five of the six patients, the increase in PaO2 differed between sides, suggesting asymmetric lung disease. Continuous rotation did not significantly alter the PaO2 from the supine values in these patients. Adverse effects on oxygenation caused by positional changes may be reversed by continuous rotation using the Roto Rest kinetic bed.

Adult↗
PubMed1987

Titrating positive end-expiratory pressure therapy in patients with early, moderate arterial hypoxemia.

A prospective randomized study to compare two physiologic end-points for titrating positive end-expiratory pressure (PEEP) was performed in patients with early, moderate arterial hypoxemia after surgery or trauma. All patients initially received 5 cm H2O of PEEP. In group 1 patients, PEEP was increased only if PaO2 decreased below 65 torr on an inspired oxygen fraction (FIO2) of 0.45. PEEP was then added in 2- to 3-cm H2O increments until PaO2 again was above 65 torr. Group 2 patients were treated with incremental PEEP until the PaO2/FIO2 ratio was greater than 300 or physiologic shunt (Qsp/Qt) was less than 0.20. All therapy other than PEEP was similar in the two groups. There were no statistically significant differences in entry PaO2 (mean 85 +/- 11 [SD] and 87 +/- 11 torr in groups 1 and 2, respectively), and Qsp/Qt was 0.22 in each group. Five (28%) of 18 patients in group 1 and 19 (95%) of 20 patients in group 2 received more than 5 cm H2O of PEEP. Between groups 1 and 2 there were no statistically significant differences in days intubated (3.4 +/- 3 vs. 5.3 +/- 5, respectively), ICU days (5.3 +/- 3 vs. 6.6 +/- 5), hospitalization days (26 +/- 24 vs. 28 +/- 24), incidence of pulmonary barotrauma (0/18 vs. 1/20), ICU mortality (22% vs. 20%), or overall mortality (33% vs. 25%). The number of blood gas analyses and cardiac output measurements, and the total hospital charges were also similar in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1987

Clinical validation of a new metabolic monitor suitable for use in critically ill patients.

This report documents the validity of clinical measurements of oxygen consumption (VO2) and carbon dioxide production (VCO2) made with a new metabolic gas monitor (MGM) suitable for use in critically ill patients receiving mechanical ventilatory support. Paired samples of inspired and expired gases were obtained, and exhaled minute volume was measured in 12 patients receiving supplemental oxygen, intermittent mandatory ventilation, and PEEP. Gas volume was measured with a calibrated spirometer and oxygen and CO2 fractions were measured by mass spectrometry. Measured and derived values were compared to those obtained from the MGM connected in series with the ventilator circuit. There were no statistically significant differences between values obtained from the mass spectrometer/spirometer vs. the MGM in exhaled volume (8.60 +/- 3.81 vs. 8.58 +/- 3.72 [SD] L/min), fraction of inspired oxygen (0.451 +/- 0.011 vs. 0.452 +/- 0.010), fraction of expired oxygen (0.413 +/- 0.013 vs. 0.415 +/- 0.012), VO2 (290 +/- 113 vs. 275 +/- 88 ml/min), VCO2 (245 +/- 95 vs. 247 +/- 96 ml/min), or respiratory quotient (0.85 +/- 0.14 vs. 0.88 +/- 0.08). The fraction of expired CO2 measured by the MGM was significantly greater (0.034 +/- 0.006 vs. 0.035 +/- 0.006; p less than .001) than that measured by mass spectrometer/spirometer. Twelve additional patients were studied to compare metabolic measurements made on 45% oxygen with those made at other fraction of inspired oxygen values. There was no significant difference between values measured on 45% oxygen and those measured on 30% to 50% oxygen.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Continuous venous oximetry in surgical patients.

A prospective study was performed to evaluate the efficacy of continuous venous oximetry to supplement traditional hemodynamic monitoring in 39 critically ill surgical patients. There was no statistically significant difference in SvO2 between the continuous in vivo values and in vitro values (0.694 +/- 0.095 vs. 0.698 +/- 0.108). There was no statistically significant correlation between continuously measured SvO2 and PaO2 (r = 0.09, p greater than 0.5), SaO2 (r = 0.08, p greater than 0.5), or oxygen consumption (r = 0.46, p greater than 0.5). There was a slight but statistically significant correlation between continuously measured SvO2 and cardiac output (r = 0.40, p less than 0.025) and oxygen delivery (r = 0.49, p less than 0.005). There was a highly significant correlation between continuously measured SvO2 and oxygen utilization coefficient (r = -0.96, p less than 0.001). Continuously measured SvO2 is a reliable predictor of SvO2 measured intermittently by in vitro methods. In critically ill surgical patients, SvO2 does not correlate highly with the individual determinants of oxygen transport but rather correlates with the oxygen utilization coefficient and therefore reflects the overall balance between oxygen consumption and delivery.

Cardiac Output↗