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Biomedical subjects

L D Nelson

Publications and source records attributed to L D Nelson.

At least 55 records · Page 3Linked 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↗
PubMed1994

Re-examining threats to the reliability and validity of putative brain-behavior relationships: new guidelines for assessing the effect of patients lost to follow-up.

It often happens in behavioral and biomedical research that subjects in prospective, multiple assessment investigations, including clinical trials, are lost to follow-up evaluations. The purpose of this report is to outline a model that will enable the investigators to determine the extent to which results based upon the maintained cohort can be generalized to the attrited cohort, or those subjects lost to follow-up. While our proposed model derives from a specific application pertaining to changes in personality and affect behaviors following left and right hemisphere stroke, it should apply, with appropriate study-specific modifications, to a wide range of follow-up research designs in neuropsychology, behavioral science more generally, and other areas of biomedical research.

Bias↗
PubMed1994

Emotional sequelae of stroke: a longitudinal perspective.

This study investigated emotional change following stroke at acute (2-week), 2-month, and 6-month time intervals. Five dimensions of emotional functioning were examined in a sample of 19 stroke subjects: indifference, inappropriateness, depression, mania, and pragnosia (a defect in the pragmatics of social communicative style). Results showed that, at the 2-month point, differential recovery rates become apparent depending on hemispheric side of the stroke lesion. Increased indifference, inappropriateness, and depression appear to account for these results and suggest a slower rate of recovery on these variables in the left hemisphere group (LH n = 9) compared to the right (RH n = 10). Results further indicate that, at the 6-month point, emotional functioning in RH subjects appears to worsen. In contrast, emotional recovery in LH subjects seems to stabilize at this time. Clinical implications of these findings in terms of type and timing of intervention are discussed.

Affective Symptoms↗
PubMed1994

Ventilatory response to high caloric loads in critically ill patients.

OBJECTIVE: To assess the effect of high caloric loads on CO2 metabolism and ventilation. DESIGN: Retrospective, clinical review. SETTING: Intensive and special care units of a university medical center. PATIENTS: A consecutive series of 78 intubated patients who underwent 129 metabolic measurements as part of their nutritional support. MEASUREMENTS AND MAIN RESULTS: A total of 129 measurements of oxygen consumption, CO2 production, respiratory quotient, energy expenditure, minute ventilation, alveolar ventilation, deadspace ventilation, PaCO2, respiratory rates and volumes, and substrate intake were made in 78 critically ill patients to determine their response to caloric loads. Statistically significant differences in indexed CO2 production, exhaled minute ventilation, deadspace ventilation, and intermittent mandatory ventilation rate existed between groups of patients with respiratory quotient of > 1 or respiratory quotient of < or = 1. Total caloric and carbohydrate caloric intake were 21% greater in those patients with respiratory quotient of > 1, but this was not a statistically significant difference (p = .51). There was no significant difference between the groups for indexed oxygen consumption, alveolar ventilation, PaCO2, or measured energy expenditure. There was a correlation between carbohydrate caloric intake and CO2 production for the entire population (r2 = .31, p < .001), with the latter relationship statistically greater (p = .006) in the respiratory quotient of > 1 group (r2 = .76, p < .001) relative to the respiratory quotient of < or = 1 group (r2 = .20, p < .001). There was a correlation between carbohydrate caloric intake and alveolar ventilation (r2 = .19, p < .001) with no significant difference between the two groups. A correlation between CO2 production and exhaled minute ventilation (r2 = .25, p < .001) was present only in the respiratory quotient of < or = 1 group while a strong correlation between CO2 production and alveolar ventilation was observed for the entire population (r2 = .47, p < .001) with no difference between groups. CONCLUSIONS: Increased CO2 production, exhaled minute ventilation, and deadspace ventilation values in the overfed group and the lack of difference between alveolar ventilation, PaCO2, and measured energy expenditure, along with correlations between CO2 production and alveolar ventilation suggest that carbohydrate loads increase CO2 production which drives alveolar ventilation, thus preventing hypercapnia. When alveolar ventilation does not increase (and PaCO2 increases) or when the spontaneous breathing rate increases to augment alveolar ventilation, the clinical response of increasing mechanical ventilation may increase deadspace ventilation.

Adolescent↗
PubMed1994

Thermodilution right ventricular ejection fraction measurements: room temperature versus cold temperature injectate.

OBJECTIVE: To compare thermodilution right ventricular ejection fraction measurements using 10 mL room temperature injectate vs. 10 mL cold temperature injectate. DESIGN: Prospective, clinical study. SETTING: Adult surgical intensive care unit (ICU) in a university hospital. PATIENTS: Sixty adult surgical ICU patients requiring hemodynamic monitoring by a pulmonary artery catheter. INTERVENTIONS: Patients were in a supine position with the bed flat during thermodilution measurements. Four 10 mL room temperature injections were alternated with four 10 mL cold temperature injections. MEASUREMENTS AND MAIN RESULTS: One hundred eleven paired thermodilution right ventricular ejection fraction measurements were made in patients during a "steady state." There were no restrictions regarding body temperature, cardiac index, heart rate or rhythm. Injectate temperature was measured by an in-line temperature probe. Injections were synchronized with end-expiration of mechanical ventilator breaths. The first injection was deleted from each temperature group. Reproducibility of individual right ventricular ejection fraction measurements was assessed by calculating the mean variation of triplicate measurements in each temperature group. Mean values of room temperature measurements were compared with cold temperature measurements by Student's t-test. Linear regression analysis, bias, and precision were also calculated. There was no significant difference (p = .752) between mean right ventricular ejection fraction measurements determined with room temperature (23.9 +/- 1 degrees C) vs. cold temperature (8.0 +/- 1.1 degrees C) injectate. There was a high degree of correlation between measurements (r2 = .876, p < .001). The bias of room temperature measurements compared with cold temperature was -0.39% and the precision was +/- 3.3%. The mean variation between individual measurements in all room temperature and cold temperature right ventricular ejection fraction measurements was 9.7% and 8.0%, respectively. There was no significant difference and there was a high degree of correlation in mean right ventricular ejection fraction measurements when data were grouped according to body temperature, heart rate, cardiac index, right ventricular ejection fraction, central venous pressure, pulmonary vascular resistance index, right ventricular end-diastolic volume index, or right ventricular stroke work index. CONCLUSIONS: The results suggest that room temperature injectate may be used for right ventricular ejection fraction measurements in critically ill adult surgical patients. Utilizing room temperature injectate for right ventricular ejection fraction measurements may save time and costs in the critical care unit.

Adult↗
PubMed1994

Gastric tonometry supplements information provided by systemic indicators of oxygen transport.

HYPOTHESIS: Assessment of splanchnic perfusion by gastric intramucosal pH (pHi) adds to the information provided by systemic indicators of oxygen transport. SETTING: University Hospital level I trauma center. DESIGN: Prospective study in 20 critically ill trauma patients comparing pHi with base deficit, lactate, oxygen delivery, and oxygen consumption (indexed to body surface area), mixed venous oxygen saturation (Svo2), oxygen utilization coefficient, and arterial pH. All measurements were obtained at admission, 1, 2, 4, 8, 16, and 24 hours, or at death. MAIN OUTCOME MEASURES: Correlation of pHi with the measured systemic variables, prediction of organ dysfunction, development of multiple organ dysfunction syndrome, and mortality. RESULTS: There was a poor correlation between pHi and the systemic hemodynamic and oxygen transport variables. Patients with a low pHi (< 7.32) on admission who did not correct within the initial 24 hours had a higher mortality (50% vs. 0.0%, p = 0.03) and incidence of organ dysfunction (2.6 organs/patient vs. 0.62 organs/patient, p = 0.02) than those who did. Using logistic regression analysis, only pHi, base deficit, and Svo2 were significantly associated with mortality during the study period. At 24 hours, only pHi was different between patients who developed multiple organ dysfunction syndrome and those who did not. There was a threshold value for pHi (7.10) which identified those patients who would go on to develop multiple organ dysfunction syndrome. CONCLUSIONS: Uncorrected splanchnic malperfusion is associated with a higher incidence of organ dysfunction and mortality. Gastric tonometry supplements information provided by systemic indicators of oxygen transport during resuscitation of critically ill trauma patients.

Acid-Base Equilibrium↗
PubMed1994

Predictors of total parenteral nutrition-induced lipogenesis.

OBJECTIVE: To evaluate the incidence and cause of parenteral nutrition-induced lipogenesis. DESIGN: Retrospective patient review. SETTING: A 40-bed predominantly surgical ICU. PATIENTS: One hundred forty patients receiving central venous nutrition and mechanical ventilatory support. INTERVENTIONS: Indirect calorimetry was used to determine patient's measured energy expenditure (MEE) and respiratory quotient (RQ). Additionally total caloric intake (TCAL), glucose infusion rate, basal energy expenditure (BEE), estimated stress factor, and calculated energy expenditure (CEE) were assessed in each patient. MEASUREMENTS AND MAIN RESULTS: Net fat synthesis was found as RQs exceeded 1 in 47 percent of patients. Statistically significant differences in oxygen consumption, CO2 production, measured energy expenditure, total and carbohydrate caloric intake, and glucose infusion rate were found between groups of patients with an RQ < or = or > 1. Seventy-three percent of patients with glucose infusion rates > 4 mg/kg-min had RQs > 1. CONCLUSIONS: Net fat synthesis was found in a surprisingly large number of critically ill patients receiving central venous nutrition. Many of these patients received carbohydrate calories in excess of their measured energy expenditure, even though it appeared that they needed this level of caloric intake by clinical assessment. The high carbohydrate total parenteral nutrition (TPN) solutions with lipids provided only for prevention of essential fatty acid depletion resulted in an unacceptably high incidence of fat synthesis. The results suggest that caloric intake may be optimized in critically ill patients using indirect calorimetry. When calorimetry is not available, a total caloric intake of up to 140 percent of the BEE with glucose infusion rates not exceeding 4 mg/kg-min and fats providing 40 to 60 percent of calories will meet the energy requirements of most critically ill patients without forcing the RQ > 1.

Aged↗
PubMed1993

Re-examining handedness in schizophrenia: now you see it--now you don't.

The present study was designed to examine patterns of handedness across tasks (i.e., those requiring less vs. greater skill) and over time (initially and 1 month later) in 72 schizophrenic patients and 105 normal controls. Two important methodologic advances were introduced: (1) two handedness tasks, varying in skill level (simple vs. complex); and (2) the addition of a retest on both tasks, 1 month later. Results show a higher incidence (43%) of mixed handedness in the schizophrenic sample than in normal controls (14.3%) on tasks requiring less precision in performance. Similar results were obtained when schizophrenic patients were retested 1 month later, RI = .88. When the more demanding set of tasks was presented, the frequency of mixed handed schizophrenics dropped by 50% at initial testing. Despite these findings, there was no evidence for stability of change over time. For example, each of the most extreme shifters at Time 1 was fully lateralized 1 month later.

Adult↗
PubMed1993

Neurogenic control of renal function in response to graded nonhypotensive hemorrhage in conscious dogs.

The reflex control of plasma renin activity (PRA) and urinary sodium excretion (UNaV) was evaluated in 13 dogs instrumented for chronic study and maintained on a normal sodium intake (40 meq/day). Graded blood volume depletion of 14 (BVD1) and 21% (BVD2) of the estimated total blood volume was used to activate renal sympathetic nerve activity (RSNA), and experiments were conducted before and after bilateral renal denervation (DNX). In dogs with innervated kidneys, nonhypotensive BVD1 increased RSNA 40.9 +/- 10.9% (P < 0.05) above control. Blood volume depletion increased PRA from 1.95 +/- 0.52 to 3.5 +/- 0.57 ng.ml-1 x h-1 and decreased UNaV from 58.2 +/- 10.1 to 35.5 +/- 4.3 mu eq/min without changing renal blood flow or glomerular filtration rate. BVD2 failed to further activate RSNA (52.0 +/- 16.7%) but did increase PRA to 4.85 +/- 0.83 ng.ml-1 x h-1 and decreased UNaV to 17.9 +/- 2.7 mu eq/min. Renal DNX (n = 13) abolished both the PRA and antinatriuretic responses to BVD1 and BVD2. Thus volume-invoked reflex activation of RSNA, but not altered renal hemodynamics, mediates, activation of PRA and antinatriuresis. This neurogenic control of renal function may be critical to the rapid regulation of extracellular fluid volume, via alterations in urinary excretion.

Animals↗
PubMed1993

Role of intrarenal ANG II in reflex neural stimulation of plasma renin activity and renal sodium reabsorption.

Renal sympathetic stimulation of plasma renin activity (PRA) and sodium reabsorption was examined in conscious dogs before and during intrarenal angiotensin II (ANG II)-type 1 receptor blockade with losartan (Dup-753) and converting enzyme inhibition. In uninephrectomized dogs, renal function and PRA responses to 14% blood volume depletion (BVD) were measured. BVD was utilized to activate renal sympathetic outflow in the absence of hypotension. In eight vehicle-treated dogs, 14% BVD increased PRA from 1.38 +/- 0.32 to 2.79 +/- 0.66 ng ANG I.ml-1 x h-1 and decreased urinary sodium excretion (UNaV) from 85.1 +/- 11.3 to 45.4 +/- 7.5 mueq/min. During losartan (n = 6) and captopril (n = 5) infusion, plasma renin responses were enhanced in response to 14% BVD (1.93 +/- 0.48 to 5.74 +/- 2.25 and 3.03 +/- 0.73 to 9.19 +/- 1.94 ng ANG I.ml-1 x h-1, respectively), whereas antinatriuretic responses were similar to vehicle-infused dogs. Thus, neurogenic antinatriuresis is not mediated by secondary generation of ANG II, since UNaV decreased similarly to control in all conditions of ANG II blockade. Tonic intrarenal and/or circulating ANG II synthesis of dogs on a normal sodium diet inhibit neurogenic stimulation of renin release, since PRA responses were enhanced after blockade of ANG II.

Absorption↗
PubMed1992

Kinetic therapy in critically ill trauma patients.

OBJECTIVES: To compare the incidence of pulmonary complications and hospital resource utilisation in patients treated with continuous rotation therapy versus manual turning in a traditional hospital bed. DESIGN: Prospective, randomised clinical trial. SETTING: Surgical intensive care unit of a large, tertiary care, urban hospital. PATIENTS: One-hundred-and-thirty-seven consecutive injured patients admitted to the Surgical Intensive Care Unit were prospectively randomised to receive either the Rotorest Kinetic Treatment Table or a traditional hospital bed. One hundred of these patients met the study criteria and are the basis of this report. METHODS: The patients' medical records were reviewed in a prospective manner to determine the frequency and severity of pulmonary complications and resource utilisation in the two patient groups. MAIN RESULTS: There were no significant differences in the minimum, average, or maximum pO 2, pCO 2, PEEP, IMV rate, or pre-extubation blood gases during the first seven days of the study. Fewer cardiac output measurements, arterial blood gas measurements, chest X-rays, respiratory therapies, hours intubated, days in the ICU, days in the step-down unit, days in the hospital, and lower ICU charges, respiratory care charges, and total hospital charges were utilised in the patients treated with the kinetic bed. The incidence of pulmonary event complications and process complications was lower in the group of patients treated on the Rotorest bed.(ABSTRACT TRUNCATED AT 250 WORDS)

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↗