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Biomedical subjects

L D Nelson

Publications and source records attributed to L D Nelson.

At least 37 records · Page 2Linked to original sources

Evaluation of acute mental status change in the nonhead injured trauma patient.

Acute mental status change in the first 24 hours after trauma is uncommon in nonhead injured patients who initially present with a normal sensorium. Although arterial hypoxemia is the classic etiology for such a mental status change, three less common etiologies should always be considered: cerebral fat embolism, blunt carotid artery injury, and vertebrobasilar artery thrombosis. Prompt diagnosis and appropriate treatment can significantly improve patient morbidity and mortality. Three nonhead injured trauma patients are described illustrating cerebral fat embolism, blunt carotid artery injury, and vertebrobasilar artery thrombosis as causes of acute mental status change. Each patient initially presented with a clear sensorium, but subsequently developed neurological deficits within 24 hours after admission. All had a normal admission CT scan of the head. MRI or conventional arteriography was diagnostic in each case. Any patient who is initially lucid and subsequently develops a neurological deficit, or a patient whose neurological status does not correlate with brain CT findings should undergo immediate evaluation for possible cerebral fat embolism or cervical vessel injury. An algorithm for management of nonhead injured trauma patients with acute mental status deterioration is presented.

Accidents, Traffic↗

Estrus synchronization with an oral progestogen prior to superovulation of postpartum beef cows.

Ovarian follicular dynamics and steroid secretion patterns were monitored in postpartum beef cows that were synchronized for estrus with melengestrol acetate (MGA) or prostaglandin F(2alpha) (PGF) prior to superovulation. Twenty-four muhiparous Angus cows were stratified by number of days postpartum to an MGA or PGF treatment prior to superovulation. Cows in the MGA group were fed 0.5 mg MGA/d for 14 d in a grain carrier. Superstitnulatory treatments began 14 d after withdrawal of MGA from feed or 11 d after administering a single injection of 500 microg cloprostenol (PGF). Supersthnulatory treatments (FSH) were administered twice daily in decreasing doses (7.5, 5, 5, 2.5 mg) over 4 d. Sixty and 72 h after initiating the superstimulatory treatments, all cows were treated with 750 microg and 500 microg PGF, respectively Cows were inseminated at 0, 12, and 24 h from the onset of standing estrus with semen from 2 proven sires. Cows within treatment were inseminated with 1, 2 and 1 (single) or 2, 4 and 2 units (double) of semen at the designated insemination times. Blood sampling and transrectal ultrasonography of ovaries were performed daily beginning 2 d prior to the initiation of FSH treatment and were continued through embryo recovery. Ovaries were examined daily to determine the number and size of follicles. Plasma samples were analyzed for progesterone and estradiol. Follicles were counted and categorized based on a 5 to 9 mm range or >/= 10 mm. At the end of superovulatory treatment there were more (P </= 0.01) follicles >/= 10 mm among cows that were estrus synchronized with MGA (75 +/- 1.2) than with PGF (3.9 +/- 1.2) These differences were reflected in higher (P </= 0.05) subsequent concentrations of plasma progesterone, suggestive of differences in ovulation rate between treatments (MGA = 8.5 ng/ml; PGF = 5.6 ng/ml). There were no significant differences between treatments in concentrations of estradiol, total number of ova (MGA = 11; PGF = 9), fertilized embryos (MGA = 9; PGF = 7), or transferable embryos recovered (MGA = 8; PGF = 6) Furthermore, double insemination offered no significant improvement in the number of recovered fertilized ova. These data identify differences in follicular and endocrine response when cows were estrus synchronized with MGA versus PGF prior to superovulation.

Journal Article↗

Ingested IFN-alpha has biological effects in humans with relapsing-remitting multiple sclerosis.

Parenterally administered human recombinant type I interferons (hrIFN) in relapsing-remitting multiple sclerosis (RRMS) decrease relapses and spontaneous in vitro IFN-gamma production, reduce clinical progression, and decrease magnetic resonance imaging (MRI)-defined disease activity and lesions. Parenterally administered type I IFN use is limited by clinical and chemical toxicities, and the induction of antibodies that abrogate their activity in vivo correlated with the loss of clinical benefit. Therefore, we determined whether ingested IFN-alpha was non-toxic and had biological effects in humans. Ingested hrIFN-alpha showed no toxicity in normal volunteers or patients with RRMS at doses ranging from 300 to 100,000 units. In subjects with RRMS, a significant decrease in Con A-mediated proliferation and serum soluble intercellular adhesion molecule-1 (sICAM-1), a surrogate measure for disease activity in MS, was found after ingesting 10,000 and 30,000 units IFN-alpha The RRMS subjects also showed decreased IL-2 secretion after ingesting 10,000 units IFN-alpha and decreased IFN-gamma, TGF-beta and IL-10 production after ingesting 30,000 units IFN-alpha. The decreased secretion of IFN-gamma and IL-2 by ingested IFN-alpha suggests that oral IFN-alpha may cause a functional inhibition of Th J-like T helper cells in RRMS, a potential site of intervention at the level of effector T cells in MS. Our studies support the oral use of human IFN-alpha as a biological response modifier in humans.

Administration, Oral↗

IFN-beta 1b treatment of relapsing multiple sclerosis has no effect on CD3-induced inflammatory or counterregulatory anti-inflammatory cytokine secretion ex vivo after nine months.

Multiple sclerosis (MS) is presumed to be a T-cell mediated chronic inflammatory disease of the central nervous system. We have previously reported that IFN-beta 1b (Betaseron) decreases CD3-mediated TNF-alpha secretion but increases another inflammatory cytokine, IL-6 after three months of treatment. We have now examined cytokine secretion of peripheral blood mononuclear (PMNC) cells after stimulation with OKT3 (anti-CD3) monoclonal antibody (mAb) or Con A in subjects with clinically stable relapsing MS before and three, six and nine months after initiating IFN-beta 1b treatment. At nine months Con A-induced TNF-alpha secretion decreased significantly below baseline but IFN-gamma secretion increased above baseline. There were no significant changes in Con A-induced IL-4 over the six month period and no changes in IL-10 and IL-2 over the nine month period. After nine months on treatment the CD3-induced TNF-alpha and IFN-gamma secretion was not significantly different from the original baseline values. Increased CD3-mediated IL-6 secretion in on-treatment compared to pre-treatment samples at three months gradually declined to baseline values by nine months on-treatment. There was no significant changes from baseline compared to nine months on-treatment in CD3-mediated IL-2, IL-4, IL-10. IFN-beta 1b (Betaseron) treatment has no clear persistent effect on CD3-induced inflammatory or counterregulatory anti-inflammatory cytokine secretion.

Adult↗

Increased in vitro induced CD4+ and CD8+ T cell IFN-gamma and CD4+ T cell IL-10 production in stable relapsing multiple sclerosis.

Multiple sclerosis (MS) is presumed to be a T-cell mediated chronic inflammatory disease of the central nervous system. Investigators previously demonstrated increased IFN-gamma (pro-inflammatory) and IL-10 (counterregulatory anti-inflammatory) in MS. The balance of pro-inflammatory and counterregulatory anti-inflammatory cytokines may be important in the stabilization of disease activity. Purified CD4+ and CD8+ T cells from patients with clinically definite, stable relapsing MS (RRMS) were stimulated by anti-CD3 mAb or Con A for 48 hours and cytokine supernatants analysed for production of IL-2, IL-6, IFN-gamma, TNF-alpha (potential pro-inflammatory) and IL-4, IL-10, and TGF-beta (potential counterregulatory anti-inflammatory). Con A activated CD4+ and CD8+ T cell proinflammatory cytokine IL-2 secretion, CD4+ T cell IL-6 secretion, CD4+ and CD8+ T cell TNF-alpha secretion and CD8+ T cell IFN-gamma secretion was decreased significantly in RRMS subjects compared to controls. CD3 activated CD4+ and CD8+ T cell IL-6 secretion and CD4+ T cell TNF-alpha secretion was significantly decreased in MS subjects compared to controls. In contrast, there was increased CD3-induced IFN-gamma in both CD4+ and CD8+ T cells and counterregulatory anti-inflammatory CD3-induced IL-10 secretion in CD4+ T cells in RRMS compared to controls. These data suggest that an equilibrium of a pro-inflammatory (IFN-gamma) and a counterregulatory anti-inflammatory (IL-10) cytokine may define stable clinically definite early RRMS.

CD3 Complex↗

The new pulmonary artery catheters: continuous venous oximetry, right ventricular ejection fraction, and continuous cardiac output.

OBJECTIVE: To review the literature addressing the new pulmonary artery catheters: continuous venous oximetry, right ventricular ejection fraction, and continuous cardiac output. DATA SOURCE: All pertinent English language literature dealing with new pulmonary artery catheters were retrieved from 1981 through 1996. STUDY SELECTION: Articles were chosen for review if the primary objective of the paper was study or review of technology related to new pulmonary artery catheters. DATA EXTRACTION: From the literature selected, information was obtained about continuous venous oximetry, right ventricular ejection fraction, and continuous cardiac output catheters. DATA SYNTHESIS: When pulmonary artery catheterization is used, continuous venous oximetry catheters may be considered for use when it is anticipated that therapy will be based upon oxygen transport end points. When pulmonary artery catheterization is used, right ventricular ejection fraction catheters may be considered for use when the anticipated therapy will be based upon evaluation of ventricular preload and when central venous pressure and/or pulmonary artery occlusion do not accurately reflect preload. When pulmonary artery catheterization is used, continuous cardiac output catheters may be considered for use in titration of interventions employed to alter stroke volume. CONCLUSION: Clinician misinterpretation and misapplication of the data appear to be the greatest impediment to using pulmonary artery catheterization to alter pathophysiologic processes and improve outcome in critically ill patients. Future research should first document effectiveness or lack of effectiveness of the "standard" pulmonary artery catheter (PAC). Pending these results, outcome and cost/benefit studies should be performed comparing "standard" with new PACs.

Cardiac Output↗

Preload assessment in trauma patients during large-volume shock resuscitation.

OBJECTIVES: To evaluate the utility of the right ventricular end-diastolic volume index (RVEDVI) as a method of preload assessment in trauma patients during large-volume shock resuscitation, and to compare the RVEDVI with the pulmonary artery occlusion pressure (PAOP) as a predictor of preload in this patient population. DESIGN: Retrospective study of a consecutive series of 46 trauma patients, admitted between June 1, 1992, and June 1, 1993, who received a volumetric oximetry pulmonary artery catheter and greater than 10 L of fluid in 24 hours. SETTINGS: University level 1 trauma center. MAIN OUTCOME MEASURES: Correlations of the RVEDVI and PAOP with the cardiac index (CI) during the defined study period. RESULTS: Three hundred fourteen measurements of the RVEDVI, PAOP, CI, and other hemodynamic variables were evaluated. Patients received a mean +/- SD of 22.1 +/- 13.3 L of blood and fluid during the 24 hours. The RVEDVI correlated better (P < .001) with the CI (r = 0.39) than did the PAOP (R = 0.05). Furthermore, there was a better correlation (P < .04) between the RVEDVI and CI when the RVEDVI was 130 mL/m2 or less (r = 0.54) than when it was greater than 130 mL/m2 (r = 0.30). CONCLUSIONS: The RVEDVI is a better predictor of preload than the PAOP in trauma patients during large-volume shock resuscitation. When the RVEDVI is 130 mL/m2 or less, volume administration will likely increase the CI.

Adult↗

High-inflation pressure and positive end-expiratory pressure. Injurious to the lung? No.

Survival rates in ARDS with conventional ventilation using high oxygen fractions and low PEEP levels have been reported to be less than 10%. In three prospective evaluations of ARDS in the 1980s, mortality rates remained greater than 60%. Early studies using high-level PEEP therapy in severe ARDS by Douglas, Downs, Kirby, and Civetta showed improved survival rates with ranges between 60% and 80%. In 1979 Gallagher reviewed 59 patients with ARDS who were treated with PEEP greater than 15 cm H2O titrated to improve FRC by achieving an intrapulmonary shunt fraction of 15%. The overall survival was 65%, with only 5% of the patients dying secondary to respiratory failure. In the more recent study by Miller in trauma patients and later by DiRusso in a variety of surgical patients, the overall mortality rate for those patients receiving PEEP greater than 15 cm H2O was 20% to 30%. Of the 14 patients who died, only seven (10% of the total) succumbed to respiratory failure. The remaining patients died from the primary underlying disease with normal oxygenation or after significant weaning from high PEEP levels. By using a goal-oriented approach to the management of patients with severe ARDS, we have found that high-level PEEP therapy was effective in lowering the intrapulmonary shunt and improving the SaO2 at acceptable levels of inspired oxygen. All of these patients were ventilated with traditional high tidal volumes (10 to 15 mL/kg) and therefore exhibited high peak inspiratory airway pressures. This support method did not seem to cause lung injury or an excessive amount of barotrauma in these patients, but in fact, was associated with a lower mortality rate (30%) than reported in other studies of patients with lesser degrees of lung oxygenation dysfunction and extrapulmonary organ system dysfunction. Currently available information indicates that increases in mean airway pressure (induced with PEEP or other modes of ventilatory support to restore losses in FRC that occur during ARDS) and limiting exposure to toxic concentrations of oxygen minimize ventilator-induced secondary lung injury and maximize chances for survival. Arbitrary limitations of peak inspiratory or end-expiratory airway pressure or mandatory tidal volume in patients with severe ARDS seem to be unfounded. Failure to achieve adequate physiologic end-points in these patients may increase morbidity and mortality rates.

Barotrauma↗

The new pulmonary arterial catheters. Right ventricular ejection fraction and continuous cardiac output.

The flow-directed pulmonary artery catheter is the mainstay of hemodynamic monitoring in critically ill and injured patients. During its 25-year history, the catheter has been modified to measure mixed venous oxygen saturation, right ventricular ejection fraction, and recently, continual thermodilution cardiac output. The clinical application of the new generations of pulmonary artery catheters is reviewed in this article.

Cardiac Output↗

Characterization of sodium-calcium exchange in rabbit renal arterioles.

Experiments were performed to test the hypothesis that renal arterioles exhibit Na-Ca exchange capability and that this process is regulated by protein kinase C (PKC). Glomeruli with attached arterioles were dissected from rabbit kidney and loaded with fura-2 for measurement of intracellular calcium concentration ([Ca2+]i) using microscope-based photometry. In tissue bathed in Ringer's solution containing 150 mM Na+ and 1.5 mM Ca2+, afferent and efferent arteriolar [Ca2+]i averaged 136 +/- 6 and 154 +/- 7 nM, respectively. Removal of extracellular Na+ increased afferent arteriolar [Ca2+]i by 70 +/- 7 mM, while efferent arteriolar [Ca2+]i only increased by 39 +/- 5 nM (P < 0.01 vs. afferent arteriole). These responses were inhibited by 6 nM Ni2+ and required extracellular Ca2+, but were unaffected by 10 microM diltiazem. After incubation in 500 microM ouabain, 5 microM monensin, and 5 microM nigericin, [Ca2+]i responses to removal of extracellular Na+ were exaggerated significantly, averaging 174 +/- 50 nM in afferent arterioles and 222 +/- 82 nM in efferent arterioles (NS vs. afferent arterioles). Moreover, responses to removal of extracellular Na+ were enhanced by 100 nM phorbol 12-myristate 13-acetate, an affect which was blocked by PKC inhibition (25 nM K252b). These data indicate that both afferent and efferent arterioles express the Na-Ca exchanger, and that PKC activity impacts on exchange capacity in these vessels.

Animals↗

Altered sodium-calcium exchange in afferent arterioles of the spontaneously hypertensive rat.

Studies were performed to determine if there is a derangement in Na-Ca exchange activity in afferent (AA) and efferent (EA) arterioles from 3- and 9-week-old spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. Cytosolic calcium concentration ([Ca2+]i) was assessed using microscope-based photometry in fura-2 loaded arterioles bathed in a Ringer's solution. Baseline [Ca2+]i was similar in the AA of 3- and 9-week-old WKY and SHR. In AA from 3-week-old rats, [Ca2+]i increased by 89 +/- 15 nM in WKY and by 73 +/- 13 nM in SHR during decreases in bath sodium concentration ([Na+]e) from 150 to 2 mM (Na+ replaced with n-methyl-D-glucamine). In 9-week-old hypertensive SHR (SBP = 150 mm Hg), increases in [Ca2+]i were attenuated (24 +/- 3 nM) relative to 3-week-old WKY and SHR, and 9-week-old WKY (90 +/- 9 nM; P < 0.05). Likewise, the rate of removal of Ca2+ in the continued presence of 2 mM Nae (Ca2+ sequestration and/or extrusion) was markedly reduced in AA of 9-week-old SHR (-0.15 +/- 0.03 nM/second) versus 3-week-old SHR (-0.72 +/- 0.12 nM/second) and 3- and 9-week-old WKY (-0.49 +/- 0.10 and -0.67 +/- 0.14 nM/second). In other experiments, AAs were preincubated in 1 mM ouabain to increase intracellular [Na+]. This maneuver augmented the increase in [Ca2+]i obtained with removal of Na+e; however, the responses obtained in 9-week-old SHR arterioles were still attenuated compared to those obtained in arterioles for 3- and 9-week-old WKY and 3-week-old SHR. These results suggest that exchanger number and/or sensitivity to the transmembrane Na gradient was reduced in the SHR AA. In EA, baseline [Ca2+]i was similar in 3- and 9-week-old WKY and SHR. In contrast to AA, the magnitude of Na-dependent and Na-independent changes in [Ca2+]i was not different in the EA of 3- and 9-week-old WKY and SHR. These results indicate that regulation of Na-Ca exchange activity may differ between AA and EA segments. Furthermore, diminished Na-Ca exchange and Na-independent Ca2+ sequestering/extrusion mechanisms could contribute to altered AA [Ca2+]i in the SHR.

Animals↗

2-Hydroxydesipramine and desipramine plasma levels: how are they related to antidepressant response?

Thirty-six outpatients aged 20 to 51 with RDC primary major depressive disorder (MDD) completed a 5-week trial of desipramine following a week of single-blind placebo. Five had a past history of hypomanic disorder. For all but one patient, daily dosage at bedtime was constant for the final 4 weeks, with a mean (S.D.) of 168.1 (46.5) mg. Plasma samples drawn at the three final weekly visits were assayed by high-performance liquid chromatography for 2-hydroxydesipramine (2-OH-DMI) and desipramine. Mean (S.D.) plasma levels were 59.8 (30.0) ng/ml for 2-OH-DMI and 142.9 (138.6) ng/ml for desipramine. Thirteen patients (36%) had a final 17-item Hamilton depression rating < and = 6 and were classified as responders. According to receiver operating characteristics analysis, patients with plasma 2-OH-DMI levels > and = 58 and < 92 ng/ml had a greater likelihood of responding than those with lower or higher levels (p = 0.005, Fisher's exact test), while patients with plasma desipramine levels > and = 64 ng/ml were more likely to respond than those with lower levels (p = 0.032, Fisher's exact test). Results using an alternate response criterion were similar. These findings suggest that in desipramine-treated outpatients with primary MDD the relationship between therapeutic response and plasma levels is curvilinear for 2-OH-DMI and linear for desipramine.

Adult↗

High-level positive end expiratory pressure management in the surgical patient with acute respiratory distress syndrome.

Although the exact incidence of ARDS is not know, it is frequently reported that there are 150,000 cases in the United States each year. Despite major advances in medical and respiratory intensive care, the mortality for patients with ARDS remains exceedingly high and has not changed appreciably from the 50% to 75% reported during the last 25 years. Currently there is no widespread, acceptable, specific therapeutic approach or agent available for the prevention or treatment of ARDS. Clinical management remains entirely supportive in nature. Although most practitioners agree that patients with severe ARDS require mechanical ventilation to maintain adequate gas exchange, controversies center on the amount of supplemental oxygen, level of positive end expiratory pressure (PEEP), and mode of ventilation needed to increase patient survival but reduce ventilator-associated complications. This review provides supportive evidence for the use of high-level PEEP (more than 15 cm H20) in the care of the surgical patient with severe ARDS.

Critical Care↗

Deep vein thrombosis in lumbar spinal fusion: a prospective study of antiembolic and pneumatic compression stockings.

We prospectively studied the incidence of deep vein thrombosis (DVT) of the thigh in 117 patients having posterior lumbar spinal fusion with instrumentation and bone grafting for degenerative disk disease or spondylolisthesis. Patients with neoplasm, infection, trauma, or history of DVT were excluded. Patients were randomized into two groups. In the operating room, group 1 patients were placed in thigh-high antiembolic compression stockings (TED hose), and group 2 patients were placed in antiembolic stockings and pneumatic compression stockings. In both groups, the stockings were used until discharge. Postoperatively, patients in both groups received 600 mg buffered aspirin twice daily. Comparative analysis of the two groups showed no difference in operative time, blood loss, number of levels of lumbar vertebrae fused, time to mobilization, weight, age, or sex. All patients had duplex scanning of the thigh postoperatively. No patient in the series was observed to have acute DVT by clinical examination or by ultrasonography.

Adult↗

Ventilatory support of the trauma patient with pulmonary contusion.

Pulmonary contusion is a common clinical condition seen in patients with thoracic trauma. The mortality rate from isolated pulmonary contusion is low, but when combined with other severe injuries patients with pulmonary contusion can have mortality rates as high as 10% to 57%. Early aggressive mechanical ventilatory support can prevent progressive atelectasis and worsening of arterial oxygenation. Careful titration of ventilatory support to physiologic end points is a reasonable approach. Unfortunately, data comparing the means of achieving the end points are lacking and no published prospective, randomized trials demonstrate superiority of any particular mode of support. Careful attention to detail and physiologic management of the patient in a goal-directed fashion using a multidisciplinary team approach involving the respiratory care practitioner, nurse, and physician is the current state of the art in the management of patients with pulmonary contusion.

Contusions↗