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Biomedical subjects

J L Rodriguez

Publications and source records attributed to J L Rodriguez.

At least 91 records · Page 5Linked to original sources

Relationship of the proinflammatory cytokines to myocardial ischemia and dysfunction after uncomplicated coronary revascularization.

The proinflammatory cytokines have been implicated in mediating myocardial dysfunction associated with myocardial infarction, severe congestive heart failure, and sepsis. We tested the hypothesis that cytokine levels are elevated after uncomplicated coronary artery bypass grafting and associated with episodes of postoperative myocardial ischemia and dysfunction. Coronary artery bypass grafting was performed under general anesthesia with moderate systemic hypothermia and cold-blood potassium cardioplegic solution. Tumor necrosis factor-alpha and interleukin-6 levels were determined by bioassays, and interleukin-8 levels were measured by a sandwich enzyme-linked immunosorbent assay. Myocardial function and ischemic episodes were assessed by intraoperative transesophageal echocardiography and perioperative 12-channel Holter monitoring. A total of 22 patients were studied, with no deaths or complications. Arterial tumor necrosis factor-alpha rose in a bimodal distribution, peaking at 2 and 18 to 24 hours after the operation (at 20.2 +/- 6.4 pg/ml, [mean +/- standard error of the mean]) and 5.8 +/- 1.6 pg/ml, respectively; before cardiopulmonary bypass: 0.90 +/- 0.20 pg/ml, p < 0.001 for both peaks) then progressively declined to levels before bypass. Arterial interleukin-6 was maximally elevated immediately on termination of cardiopulmonary bypass and peaked again 12 to 18 hours after cardiopulmonary bypass (at 7520 +/- 2439 pg/ml and 6216 +/- 1928 pg/ml, respectively; before bypass: 746 +/- 187 pg/ml, p < 0.0001 for both peaks). Arterial interleukin-8 levels were more variable but followed a similar pattern, peaking in the early period after cardiopulmonary bypass and again at 16 to 18 hours after the operation (at 4110 +/- 1403 pg/ml and 1760 +/- 1145 pg/ml, respectively; before bypass: 461 +/- 158, p < 0.05 for both peaks). By multivariate analysis, the aortic crossclamp time was independently predictive of postoperative cytokine levels. Left ventricular wall motion abnormalities were associated with both interleukin-6 and interleukin-8 levels, worsening scores being associated with increasing levels (for interleukin-6, p = 0.003; for interleukin-8, p = 0.05). Postoperative myocardial ischemic episodes were associated with interleukin-6 levels, six of seven (85%) patients with episodes of myocardial ischemia after a peak in interleukin-6 concentrations (p < 0.01). We conclude that proinflammatory cytokines are elevated after uncomplicated coronary revascularization and may contribute to postoperative myocardial ischemia and segmental wall motion abnormalities.

Aged↗

Acute skin injury releases neutrophil chemoattractants.

BACKGROUND: Progressive or ongoing skin necrosis after traumatic injury is well known. Experimental evidence has associated these events with neutrophil activation and secondary oxidant injury. To determine the mechanism by which neutrophils migrate to a site of injury, cytokine release from injured skin was measured. METHODS: Twenty-five skin biopsy specimens of acute partial thickness skin injuries were compared with uninjured skin of the same patient. Conditioned medium from explanted skin was assayed for tumor necrosis factor (TNF), interleukin-6 (IL-6), and IL-8. RESULTS: Acute skin injury resulted in a significant release of IL-8 but not IL-6 or TNF. In eight patients gradient cytokine release was found; IL-8 levels for partial thickness burn were 26.4 ng/ml, for unburned skin adjacent to the burn were 2.1 ng/ml, and for distal normal skin were 0.2 ng/ml. CONCLUSIONS: IL-8 is released from acutely injured skin; IL-6 and TNF are not. This selective release suggests a mechanism whereby neutrophils are recruited into injured tissue. These neutrophils might then induce further injury, increasing the extent of posttraumatic tissue loss.

Acute Disease↗

Geriatric trauma: aggressive intensive care unit management is justified.

The United States population older than 65 years increased 21 per cent from 1980 to 1990. Attempts to characterize geriatric trauma have failed to yield a consensus on basic descriptors or physiologic parameters predictive of outcome. We reviewed the records of 170 trauma patients, aged 60 or above, admitted to our institution in a recent 50-month period. Mortality was 21.8 per cent. None of the 54 general care patients died; 79 (68%) of the 116 ICU patients survived. ICU deaths correlated with number of organ systems failing and severe head injury. Although these results justify aggressive ICU treatment, average hospital stay was 15 days, and one third of patients required skilled nursing facilities for ultimate recovery, so the resource cost is high.

Aged↗

Traumatic rupture of a cervical parathyroid adenoma.

BACKGROUND: Spontaneous rupture of a hyperplastic parathyroid gland or adenoma resulting in extracapsular hemorrhage is extremely rare. METHODS: We report a case of traumatic rupture of a cervical parathyroid gland adenoma. RESULTS: The patient had progressive stridor, neck swelling, and chest and back pain with evidence of ongoing blood loss resulting in airway compromise. Exploration of the neck and superior mediastinum revealed hypercellular parathyroid tissue consistent with adenoma or hyperplasia. CONCLUSIONS: Traumatic rupture of an enlarged parathyroid gland is a distinct and potentially lethal cause of unexplained cervical or mediastinal hemorrhage after blunt neck trauma. Failure to consider the diagnosis may result in delayed operative intervention with persistent hemorrhage resulting in airway compromise.

Adenoma↗

Anaphylaxis after ingestion of beignets contaminated with Dermatophagoides farinae.

A 48-year-old man was evaluated for anaphylaxis associated with ingestion of beignets prepared from a commercial mix. Microscopic examination of the patient's beignet mix revealed live Dermatophagoides farinae. Another unopened box from the same source was not infested. Skin test results to aeroallergens and foods, including all beignet mix ingredients, were positive only to D. farinae and D. pteronyssinus extracts. Skin prick test results to an infested mix extract (1:5 wt/vol) were also positive, but no reaction was observed with noninfested mix extract. ELISA inhibition studies demonstrated significant inhibition of the patient's serum binding to D. farinae strips by infected mix extract. Parallel inhibition curves were produced by the infested mix extract and a commercial D. farinae extract. Noninfested mix extract showed no inhibition. RAST analysis with beignet mix discs showed significant binding of the patient's serum IgE to infested mix discs but not to noninfested mix discs. RAST inhibition studies revealed more than 86% inhibition of binding of the patient's IgE to infested mix discs by infested mix extract and D. farinae extract. No inhibition was observed with noninfested mix or 5% fetal calf serum-phosphate-buffered saline. We conclude that the allergen to which the patient reacted was most likely D. farinae and that ingestion of D. farinae may cause anaphylaxis in sensitive persons.

Allergens↗

Hospital-acquired gram-negative pneumonia in critically ill, injured patients.

Hospital-acquired gram-negative pneumonia is a major problem in critically ill, injured patients. The currently available therapeutic interventions to prevent the disease process are of limited usefulness. This most likely reflects an incomplete understanding of the complex pathophysiologic mechanism and thus invites examination of alternative mechanisms. We have hypothesized that the lung's response to traumatic injury may be driving the local organ injury by generating an early, local pulmonary cytokine production independent of the systemic cytokine response or the intensive care unit environment. Understanding the local pulmonary cytokine response to traumatic injury and its effect on the pulmonary airspace's immunologic contents may yield targeted and clinically relevant therapeutic interventions. Currently, the successful treatment of hospital-acquired gram-negative pneumonia depends on a clear and consistent definition of the disease process, knowledge that therapy with a single antibiotic is effective, and use of a concise treatment protocol that provides for reassessment of the patient when antibiotic therapy appears to be ineffective.

Critical Illness↗

Correlation of the local and systemic cytokine response with clinical outcome following thermal injury.

Eighty-eight patients with acute thermal injury were evaluated. Forty-eight hours after injury, TNF, IL-6, and IL-8 were significantly present in the systemic circulation, lung, normal skin, and thermally injured skin. The presence of TNF, IL-6, and IL-8 proteins in the lung, normal skin, and thermally injured skin were associated with TNF, IL-6, and IL-8 mRNA upregulation. Logistic regression analysis controlling for the Abbreviated Burn Severity Index demonstrated that the presence of IL-8 in the lung was associated with early pulmonary physiologic dysfunction (p = 0.006) and nosocomial pulmonary infection (p = 0.040). We conclude that acute thermal injury initiates an early systemic, lung, and skin response involving TNF, IL-6, and IL-8. The TNF, IL-6, and IL-8 protein present in the lung and skin in response to acute thermal injury are generated locally and do not originate from the systemic cytokine pool. The lung cytokine response to acute thermal injury may initiate local organ failure.

Adult↗

Lymphocyte subset responses to trauma and sepsis.

One hundred five trauma patients admitted to three trauma centers with injury Severity Scores of 20 or greater had lymphocyte phenotypic subsets characterized throughout their hospital course. Total lymphocytes, pan-T (CD2), helper T (CD4), suppressor T (CD8), pan B (CD20), and DR expressing lymphocytes were quantitated by monoclonal antibodies and flow cytometric analysis. Results were analyzed between three patient groups: uninfected, uneventful recovery (n = 64); major infection (n = 26); and dead (n = 15; 7 with sepsis). A significant lymphopenia, maximal at 3 days, occurred in the first postinjury week compared with controls (p < 0.05), which recovered over the study period. A hierarchical distribution was found between the three outcome groups with the lowest numbers of several lymphocyte phenotypes in those who died. T helper and suppressor cells were similarly affected, but lowest in patients destined to develop infection or die. The helper-suppressor ratio, however, was similar in all three outcome groups. Therefore, modulation early after injury aimed at restoring these subsets may reduce the risk of subsequent infection.

Adolescent↗

Phenotypic differences in cytokine responsiveness of hypertrophic scar versus normal dermal fibroblasts.

The alteration of normal dermal fibroblast function that leads to the development of hypertrophic scar after thermal injury is unknown. To determine functional differences that might explain this process, fibroblasts were cultured from biopsies of post-thermal injury mature hypertrophic scars and patient-matched normal skin. The mitogenic responses of scar cells to fetal bovine serum, epidermal growth factor (EGF), platelet-derived growth factor (PDGF), and tumor necrosis factor alpha (TNF alpha) were determined and compared to normal skin cells. Collagen synthetic rate was also compared in the presence and absence of transforming growth factor beta 1 (TGF beta 1). Whereas both scar and normal cells responded with increased thymidine uptake to serum and cytokines, the stimulation to EGF and serum was significantly lower in scar cells. In contrast, synthesis of collagen, but not of non-collagenous proteins, was increased in scar relative to normal cells, both basally and when stimulated with low doses of TGF beta 1. Additionally, the fraction of protein synthesized as collagen was significantly higher in scar fibroblasts. These results suggest that fibroblasts from hypertrophic scars demonstrate stable phenotypic differences in cytokine responsiveness in comparison to cells from unaffected skin. The increased rate of collagen synthesis and decreased responsiveness to mitogens are consistent with the increased extracellular matrix content and decreased cellularity of hypertrophic scars.

Adolescent↗

Control of hemorrhage during renal failure with triglycyl-lysine-vasopressin.

A 35-year-old man with chronic renal failure developed toxic epidermal necrolysis due to combination antibiotic therapy for a community acquired pneumonia. During wound care for his toxic epidermal necrolysis, he developed massive bleeding, a 4 to 6 unit blood loss at each dressing change, due to uremia-associated platelet dysfunction and thrombocytopenia. After failure of standard therapy, the man was treated with intravenous triglycyl-lysine-vasopressin, a selective peripheral vasoconstrictor. Transfusion requirements stopped during treatment. This man went on to full recovery with complete wound healing. Triglycyl-lysine-vasopressin effectively reduced skin blood loss in this man with toxic epidermal necrolysis and an intrinsic hemostatic defect, and may be useful in other patients with cutaneous blood loss.

Adult↗

A randomized prospective clinical trial to determine the efficacy of interferon-gamma in severely injured patients.

Many aspects of the normal immune response are depressed after severe injury. Reduced monocyte human leukocyte antigen-DR (HLA-DR) levels have closely correlated with the development of major infection. After a pilot study with recombinant interferon-gamma (rIFN-gamma) showed restoration of depressed HLA-DR levels after major injury, a multicenter, prospective, randomized, double-blind trial was conducted. Two hundred thirteen trauma patients who were at high risk of infection received either placebo or rIFN-gamma (100 micrograms) subcutaneously each day for 10 days after admission. One hundred ninety-three patients were evaluable with respect to primary end points. Patients treated with rIFN-gamma were older (p = 0.10) and had more severe modes of injury (p = 0.02). By the third day, both monocyte HLA-DR antigen expression and outcome predictive score were significantly better in the rIFN-gamma-treated group than in the placebo group (p = 0.0001 and p = 0.0006, respectively). Nine deaths occurred in patients treated with rIFN-gamma compared with 12 deaths in the placebo group (p = 0.46). Major infections requiring surgical drainage or debridement occurred in 17 patients treated with rIFN-gamma compared with 22 treated with placebo. No difference between treatment arms was noted in overall major or minor infection rates, but there were fewer severe infections that required reoperation or computer tomographic-guided drainage in patients receiving IFN-gamma. While these results suggest that rIFN-gamma may be useful in some aspects of infection in the patient with severe trauma, a larger trial with longer treatment will be needed to prove the comprehensive value of rIFN-gamma.

Adult↗

Early experience with adult extracorporeal membrane oxygenation in the modern era.

In 1980 we stopped using extracorporeal membrane oxygenation for adults because only 1 of 20 patients treated between 1973 and 1979 survived. In October 1988 we returned to adult extracorporeal life support (ECLS) with a modified protocol including venovenous access when possible, large oxygenators for CO2 clearance, activated clotting time of 180 to 200 seconds, and case selection based on 90% mortality (30% transpulmonary shunt). Of 19 patients referred, 14 met criteria for ECLS. Three of these 14 patients with isolated respiratory failure died before ECLS could be started, and 1 patient refused ECLS and died. Ten were placed on ECLS for 2 to 24 days. Indications were pneumonia (3), post-cardiac operation (2), and adult respiratory distress syndrome (5). Five recovered and 5 died. The cause of early death was progressive pulmonary injury (3), hemorrhage (1), and ventricular arrhythmia (1). One late death occurred at 3 months secondary to intraabdominal complications related to liver transplantation. In conclusion, 10 adult patients with severe respiratory failure were treated with extracorporeal life support; 5 patients recovered lung function and 4 of these patients survived and were discharged to home. Surviving patients were typically younger and were placed on ECLS early in their disease process, emphasizing that early intervention is one key factor to a successful outcome.

Adolescent↗

Effects of disodium octaborate tetrahydrate on survival, behavior, and egg viability of adult muscoid flies (Diptera: Muscidae).

Disodium octaborate tetrahydrate (Na2B8O13(.)4H2O) was mixed with sugar and fed to adult Musca domestica L. and Fannia canicularis (L.) to determine concentration-mortality relationships. LC50s (48-h exposure) were 5.7% for M. domestica and 1.0% for F. canicularis. Rates of 1 and 2% were used to test effects on M. domestica mortality and egg hatch over an 8-d period. Reduced egg hatch was evident after 1 d of feeding on the treated mixtures and was greatest (less than 10% egg hatch) after flies fed only on treated mixtures for 2 d. A partial rebound in egg hatch occurred after 3-4 d of feeding on treated diet. Sperm motility in females fed treated sugar was apparently normal. Fertile egg placed on treated poultry manure did not hatch, indicating embryonic death, which also may have been involved in the low hatch of eggs observed from treated flies. When flies were exposed to treated sugar for 2 d then returned to untreated diet, delayed mortality effects and reduced egg hatch persisted for at least 3 d. Behavioral assays (feeding) with M. domestica demonstrated that flies rejected borate-sugar mixtures in favor of sugar alone when the concentration of borate was greater than 2%. Given a choice of treated and untreated poultry manure for oviposition, flies also rejected the treated manure. The potential of borates in adult bait formulations or applied to developmental substrates for fly control is discussed.

Analysis of Variance↗

Survival and vertical distribution of larvae of Culicoides variipennis (Diptera: Ceratopogonidae) in drying mud habitats.

The ability of third and fourth instars of Culicoides variipennis (Coquillett) to survive in drying sandy loam soil was tested under simulated field conditions. Two hundred larvae were added to each of a number of soil-filled, plastic tubes, which were buried in the field and retrieved after 2, 5, and 7 d. Of 306 pupae or pupal exuviae recovered, 98.1% were in the top 2 cm of mud. Estimated larval mortality on day two ranged from 25.6 to 87.1% among three trials, and 92.3% of live larvae were in the top 2 cm. Estimated larval mortality on day 5 ranged from 81.4 to 97.2%, and 75.5% of live larvae were in the top 2 cm. On day 7 mortality was 95.2-100%, and 63% of surviving larvae were in the top 2 cm. Some larvae dispersed as deep as 7-10 cm (the maximum depth in the tests). Larval tolerance of unfavorable drying conditions may allow relic populations to persist in some situations, but probably this is of little concern in control of this species through water management in most settings.

Animals↗

Local production of interleukin-8 is associated with nosocomial pneumonia.

One hundred five (70%) of 151 patients hospitalized in the intensive care unit and undergoing mechanical ventilation had bronchial secretions that tested positive for interleukin-8 within 36 hours of admission. Arterial blood, mixed venous blood, and urine collected simultaneously all tested negative, except for 11 patients admitted with intra-abdominal septic foci. The presence of interleukin-8 in the pulmonary air space early in the course of hospitalization was significantly associated with patients with multiple injuries, the need for greater ventilatory support, the occurrence of pulmonary dysfunction, and a 66% incidence of nosocomial bacterial pneumonia. We conclude that the early local production of interleukin-8 in the lungs is an early marker of pulmonary injury and may be involved in the pathogenesis of nosocomial bacterial pneumonia.

Adult↗