Biomedical subjects
A R Mansberger
Publications and source records attributed to A R Mansberger.
Classroom instruction: "a blast".
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Immunoglobulin E and eosinophil counts are increased after sepsis in trauma patients.
OBJECTIVES: To determine the time course of plasma immunoglobulin E (IgE) concentration increases after traumatic injury, if increased IgE concentrations were related to clinical events or complications, and if increased peripheral eosinophil counts could be related to trauma, sepsis, or organ-specific complications. DESIGN: Data relating to severity of injury, clinical complications, plasma concentrations of IgE, and peripheral eosinophil counts were prospectively collected. SETTING: Trauma service, tertiary-care medical center. PATIENTS: One hundred adult trauma patients admitted to the intensive care unit. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Plasma IgE concentrations increased in most patients. However, the greatest increases were observed in patients with sepsis (p = .03), renal dysfunction (p = .04), or pneumonia (p = .02). IgE increases were not related to severity or mechanism of injury, allergy history, or age. The day of highest observed IgE concentration was related to the day of onset of sepsis (p = .012, r = .39), and occurred a mean of 3.8 days after sepsis. Most patients had increased peripheral eosinophil counts and eosinophil percentages of white blood cells during their intensive care unit stays. Eosinophil counts were greater in patients with sepsis (p < .0001), severe sepsis (p < .0001), or pneumonia (p < .002). CONCLUSIONS: Increased IgE concentrations and eosinophil counts were found after sepsis and do not appear to be related to the initial injury. Since IgE and eosinophil production are enhanced by interleukin-4 and interleukin-5, respectively, these findings suggest that T-helper lymphocyte type 2 cytokines are activated in response to sepsis after traumatic injury.
Increased plasma IgE levels in patients with sepsis after traumatic injury.
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Pharmacokinetics of reconstituted human high-density lipoprotein in pigs after hemorrhagic shock with resuscitation.
OBJECTIVES: Reconstituted human high-density lipoprotein (HDL) can inhibit lipopolysaccharide effects in vivo. The major objectives of this study were to characterize the pharmacokinetics of reconstituted HDL in a stressed large-animal model and to provide preclinical tolerance information in support of use of reconstituted HDL in humans. DESIGN: A randomized, blinded, placebo-controlled trial where each animal received either reconstituted human HDL at a dose of 100 mg/kg (apolipoprotein A-I) or placebo, immediately after hemorrhagic shock and resuscitation. SETTING: Animal laboratory. SUBJECTS: Twelve immature female swine (18 to 25 kg) were studied. INTERVENTIONS: Six to 8 days before shock and study drug administration, animals were anesthesized and catheters were placed in the external jugular vein and abdominal aorta. These catheters were secured to the dorsal surface. On the day of shock, the animals were sedated (alpha-chloralose) and 50 mL/kg of arterial blood was removed over 0.5 hr. One half hour after blood removal, shed blood was infused, which was immediately followed by study drug (reconstituted HDL or placebo), and then by 1 L of lactated Ringer's solution. MEASUREMENTS AND MAIN RESULTS: Physiologic (arterial blood pressure, heart rate, respiratory rate) and laboratory (serum chemistries, hematologic and coagulation studies, and blood gases) measurements were determined intermittently for 96 hrs after the induction of shock. Blood was collected intermittently for 48 hrs after shock for assay of apolipoprotein A-I and phosphatidylcholine in plasma. Reconstituted HDL was well tolerated and did not appear to alter the physiologic responses to shock and resuscitation. HDL transient increase in aspartate aminotransferase concentration was noted in the reconstituted group but this increase normalized by 24 hrs after drug administration. Mean apolipoprotein A-I pharmacokinetic parameters were as follows: half-life 24.5+/-5.3 (SD) hrs; clearance 41.9+/-10 mL/hr; and volume of distribution 1.39+/-0.08 L. The apparent mean half-life of phosphatidylcholine was 5.4+/-0.8 hrs. CONCLUSIONS: Reconstituted human HDL was well tolerated in animals that had undergone hemorrhagic shock with resuscitation. The apolipoprotein component of reconstituted HDL had a relatively long half-life, with distribution limited to the vascular space. These findings support the investigational use of this product in humans.
Association of interleukin-4 plasma levels with traumatic injury and clinical course.
OBJECTIVES: To determine if interleukin-4 (IL-4) could be detected in plasma of trauma patients and if IL-4 activity is associated with patterns of clinical events, complications, or outcomes. METHODS: A prospective case series conducted in a tertiary care referral center with a level I trauma center. One hundred patients admitted to the trauma intensive care unit for at least 3 days were included. Plasma concentrations of IL-4 and IgE were determined from admission to intensive care unit discharge. Data on clinical outcome were collected, including death, sepsis, severe sepsis, adult respiratory distress syndrome, pneumonia, and renal dysfunction. RESULTS: Interleukin-4 was detected in the plasma of 87 patients. Patients with an Injury Severity Score of greater than 25 had higher admission IL-4 levels (P = .03) and greater maximal IL-4 levels (P < .001). Admission hypotension (P = .04) and age 30 years or younger (P < .001) were also associated with higher admission IL-4 levels. Increases in IL-4 levels were significantly greater for patients in whom sepsis, severe sepsis, or pneumonia developed (P < .05). A low admission IL-4 level was associated with a greater incidence of nosocomial pneumonia (P < .001). Additional indirect evidence of IL-4 activation included increased plasma IgE levels. CONCLUSIONS: Anti-inflammatory cytokine mechanisms are activated after injury and are associated with the development of infectious complications (sepsis, severe sepsis, and pneumonia). Exogenous administration of interleukin-4 should be evaluated as an experimental therapeutic approach after trauma and associated sepsis.
Technetium Tc 99m sestamibi scan for localizing abnormal parathyroid glands after previous neck operations: preliminary experience in reoperative cases.
We used technetium Tc 99m sestamibi for successful preoperative localization of abnormal parathyroid glands in nine patients with hyperparathyroidism and a history of neck surgery. The intraoperative and pathological findings were correlated with the preoperative technetium-sestamibi scan results. These nine patients had had 13 previous neck operations, two for thyroid disease, and 11 for hyperparathyroidism. In the two operated on for thyroid disease, the 99mTc-sestamibi scan localized a parathyroid adenoma. In one patient, the three remaining hyperplastic parathyroid glands were localized using 99mTc-sestamibi scan. The other six patients had 10 operations for hyperparathyroidism; the 99mTc-sestamibi scan localized the remaining parathyroid glands causing hypercalcemia. In this preliminary experience, the 99mTc-sestamibi scan localized all the abnormal parathyroid glands causing hyperparathyroidism in patients who had previously had neck surgery.
Reconstituted high density lipoprotein inhibits physiologic and tumor necrosis factor alpha responses to lipopolysaccharide in rabbits.
OBJECTIVE: To determine the effect of reconstituted human high density lipoprotein (rHDL) on physiologic and cytokine responses to infusion of lipopolysaccharide. DESIGN: A blinded, randomized trial of three preparations of a purified human rHDL with apolipoprotein A-I-phosphatidyl choline-cholesterol molar ratios of 1:100:10, 1:150:10, and 1:200:0 and placebo in a rabbit lipopolysaccharide intravenous infusion model. INTERVENTIONS: Groups of six New Zealand white rabbits received either placebo or one of the three human rHDL preparations above as a single, 75-mg/kg (apolipoprotein A-I equivalent) dose intravenously over 10 minutes ending 5 minutes before the start of a 3-hour infusion of lipopolysaccharide. MAIN OUTCOME MEASURES: Mean arterial pressure, base excess, and plasma tumor necrosis factor alpha (TNF-alpha) production were determined. RESULTS: The human rHDL suppressed TNF-alpha production with the products having the highest fraction of phosphatidyl choline producing the greatest suppression of TNF-alpha production. The human rHDL 1:200:0 group maintained a low, near-baseline TNF-alpha concentration and minimal decline in mean arterial pressure and base excess throughout the lipopolysaccharide infusion in contrast to the placebo group. CONCLUSION: Reconstituted human high density lipoprotein appears to be useful in inhibiting the physiologic effects and cytokine release associated with endotoxemia and may provide adjunctive treatment for patients with gram-negative sepsis.
Preoperative imaging of abnormal parathyroid glands in patients with hyperparathyroid disease using combination Tc-99m-pertechnetate and Tc-99m-sestamibi radionuclide scans.
OBJECTIVE: To evaluate the efficacy of combined Tc-99m-pertechnetate and Tc-99m-sestamibi radionuclide scanning for imaging abnormal parathyroid glands in hyperparathyroid disease in a prospective study. SUMMARY BACKGROUND DATA: Established methods to localize abnormal parathyroid glands lack accuracy for routine use. Tc-99m-sestamibi used in conjunction with iodine-123 has excellent potential for preoperative imaging in patients with hyperparathyroid disease. An alternative method for parathyroid imaging was studied using Tc-99m-pertechnetate and Tc-99m-sestamibi. METHODS: Thirty patients with hyperparathyroid disease had Tc-99m-pertechnetate and Tc-99m-sestamibi subtraction radionuclide scanning to visualize abnormal parathyroid glands before surgery. The patients had surgery and pathologic confirmation of all parathyroid glands. RESULTS: In 23 patients with primary hyperparathyroidism, 12 of 13 solitary adenomas were visualized. Six of nine patients with diffuse hyperplasia had bilateral uptake consistent with diffuse hyperplasia. Three of nine patients had negative scans. One patient previously operated on for diffuse hyperplasia had only one gland scanned. Seven patients with renal failure-associated hyperparathyroid disease were scanned: five had bilateral uptake of Tc-99m-sestamibi consistent with hyperplasia, and two who had been previously operated on had localization of remaining abnormal parathyroid glands. CONCLUSIONS: Tc-99m-pertechnetate combined with Tc-99m-sestamibi subtraction radionuclide scanning is less cumbersome to implement than iodine-123 combined with Tc-99m-sestamibi scanning. It has a high sensitivity for imaging solitary parathyroid adenomas or persistent solitary hyperplastic glands. However it does not have the resolution necessary to delineate all parathyroid glands in diffuse hyperplasia.
Use of technetium Tc 99m sestamibi and iodine 123 radionuclide scan for preoperative localization of abnormal parathyroid glands in primary hyperparathyroidism.
The imaging methods currently used to localize the parathyroid gland in patients with hyperparathyroidism have been criticized as unreliable and even misleading. We evaluated a new imaging technique that uses technetium Tc 99m sestamibi and iodine 123. We studied 21 patients having a diagnosis of primary hyperparathyroidism and no previous parathyroid surgery. Scintigraphy to localize the abnormal parathyroid was done before operation. A solitary adenoma was localized in 14 patients. Six patients had images consistent with diffuse hyperplasia, and one patient had a dual adenoma. The surgical and histologic findings confirmed the preoperative data. The sensitivity of this method is 87.5%, the specificity is 100%, and the predictive value is 100%. This new method of preoperative localization of abnormal parathyroid glands is useful in patients having initial neck exploration for primary hyperparathyroidism.
Nonadenomatous thymic unencapsulated parathyroid tissue as a cause of persistent primary hyperparathyroidism.
Primary hyperparathyroidism may be caused by ectopic intrathymic parathyroid adenomas or hyperplastic parathyroid glands. The association of the ectopic inferior parathyroid glands and the thymus is due to their common embryologic origin from the third pharyngeal pouch. We report a case of primary hyperparathyroidism due to an unusual pathologic parathyroid gland formation: nonadenomatous thymic unencapsulated parathyroid tissue. Two unsuccessful neck exploration revealed only two normal parathyroid glands within the cervical area. Radiologic imaging studies failed to localize an ectopic parathyroid adenoma. Mediastinal exploration and thymectomy showed one small focus of unencapsulated hypercellular parathyroid tissue expanding peripherally along the septa of thymic adipose tissue. The hyperparathyroidism resolved with the surgical procedure.
Lipopolysaccharide-reactive immunoglobulin E is associated with lower mortality and organ failure in traumatically injured patients.
Antilipopolysaccharide (anti-LPS) immunoglobulin G (IgG) and IgM have been associated with protection from LPS effects in vivo. We investigated the presence of IgE and anti-LPS in 32 patients that had experienced severe traumatic injury and in 35 healthy volunteers; we also investigated whether IgE anti-LPS was associated with important clinical events. Plasma samples were collected daily from patients in the intensive care unit and on one occasion from volunteers; the samples were assayed for IgE anti-LPS. IgE anti-LPS was assayed by enzyme-linked immunosorbent assay with monoclonal anti-human IgE as the capture antibody. Detection was accomplished with biotin-labeled LPS (Escherichia coli J5 mutant) followed by streptavidin-peroxidase with 2,2'-azino(3-ethylbenzthiazoline)sulfonic acid as the substrate. The assay was demonstrated to be specific for IgE and LPS-biotin by nonreactivity of control sera with high-titer anti-LPS IgG and IgM and by inhibition with unlabeled LPS. IgE anti-LPS was detected in 1 of 35 healthy controls (2.9%) and 25 of 32 traumatically injured patients (78%) (P < 0.001). The presence of IgE anti-LPS was associated with a lower incidence of death (P = 0.026) and of renal failure (P = 0.0012). There was no apparent temporal relationship between detection of IgE anti-LPS and clinical events. IgG anti-LPS was detected more frequently in patients that were positive for IgE anti-LPS (P = 0.06) but was not associated with clinical events. The inability to detect IgE anti-LPS may be related to adverse clinical events through depletion of specific IgE due to LPS exposure after trauma or through saturation of the assay by IgE with other specificities. We have reported increased total IgE concentrations in these patients. (J.T. DiPiro, R.G. Hamilton, T. R. Howdieshell, N. F. Adkinson, and A. R. Mansberger, Ann. Surg. 215:460-466, 1992).
Impact of technetium-99m-sestamibi localization on operative time and success of operations for primary hyperparathyroidism.
Intraoperative identification of abnormal parathyroid glands during initial neck exploration for primary hyperparathyroidism is challenging and may require extensive dissection of the neck and mediastinum. We, therefore, evaluated the impact of preoperative localization with Technetium-99m-sestamibi (Tc-99m-sestamibi) and Iodine-123 radionuclide subtraction imaging on operative time and success of initial operation for primary hyperparathyroidism. From January 1989 to September 1992, 42 patients underwent neck exploration for primary hyperparathyroidism; 21 patients underwent neck exploration without preoperative radionuclide scanning, and 21 patients were operated upon following radionuclide Tc-99m-sestamibi localization. In the control group, pathologic exam revealed 15 patients had solitary adenomas, and six patients had diffuse hyperplasia. In the Tc-99m-sestamibi group, 16 patients had solitary adenomas, four had diffuse hyperplasia, and one had multiple adenomas. Analysis of patient demographic data revealed no differences between the control group and the Tc-99m-sestamibi group in mean age (56 vs 59 years), mean intact PTH levels (249 vs 234 pg/mL), mean total calcium (11.3 vs 12.0 mg/dL), and mean ionized calcium (6.19 vs 6.28 mg/dL). Comparison of operative data revealed no differences between groups in the mean number of parathyroid glands identified and biopsied per patient (3.1 vs 3.3), the mean largest diameter of the resected adenomas (19.6 vs 20.0 mm), and the number of patients requiring thymectomy, thyroid resection, retroesophageal exploration, mediastinal exploration, or carotid sheath exploration. The operative success rate was 90 per cent for the control group versus 100 per cent for the Tc-99m-sestamibi group.(ABSTRACT TRUNCATED AT 250 WORDS)
Prospective comparison of technetium-99m-sestamibi/iodine-123 radionuclide scan versus high-resolution ultrasonography for the preoperative localization of abnormal parathyroid glands in patients with previously unoperated primary hyperparathyroidism.
Surgery for primary hyperparathyroidism is successful in 95% of patients, but ectopic glands and anatomic variations in location are causes of surgical failure. The radionuclide imaging agent, technetium (Tc)-99m-sestamibi, in conjunction with subtraction iodine-123 scanning, is a new method of preoperative localization of abnormal parathyroid glands. In a study approved by the Institutional Review Board, 22 patients with primary hyperparathyroidism underwent preoperative evaluation with high-resolution ultrasonography and Tc-99m-sestamibi/I-123 radionuclide scanning for attempted localization of abnormal parathyroid glands. Results of Tc-99m-sestamibi scanning and ultrasound were correlated with surgical and pathologic findings. Of 22 patients, 16 had a solitary parathyroid adenoma, 1 had a double adenoma, and 5 had diffuse parathyroid hyperplasia. The Tc-99m-sestamibi/I-123 radionuclide scan preoperatively identified a solitary adenoma in 14 of 16 patients (sensitivity: 88%). However, when the data were analyzed retrospectively along with surgical and pathologic findings, the Tc-99m-sestamibi scan correctly localized all parathyroid adenomas for a sensitivity of 100%. The one patient with a double adenoma had a localization image consistent with two enlarged glands. All patients with diffuse parathyroid hyperplasia had Tc-99m-sestamibi imaging consistent with diffuse hyperplasia, although delineation of individual enlarged glands was not possible. High-resolution ultrasound identified 11 of 16 parathyroid adenomas (sensitivity: 69%). The patient with a double adenoma had a negative ultrasound. Ultrasound was less accurate in five patients with diffuse hyperplasia: one scan was completely negative, two scans revealed only one enlarged gland, and two scans revealed two enlarged glands. The Tc-99m-sestamibi/I-123 subtraction radionuclide scan is more sensitive than high-resolution ultrasonography for the preoperative localization of abnormal parathyroid glands. Tc-99m-sestamibi/I-123 radionuclide scanning may be more useful than ultrasonography to the surgeon in the preoperative localization of abnormal parathyroid glands.
Surgical embryology and anatomy of the thyroid and parathyroid glands.
A thorough knowledge of parathyroid embryology and anatomy is essential for maximum success in restoration of calcium homeostasis in those patients who have a form of hyperparathyroidism. In fact, an initial meticulous neck dissection by a competent parathyroid surgeon who is well versed in the embryology and anatomy of the neck is the current "hi tech" method of choice for parathyroid gland localization.
Total IgE in plasma is elevated after traumatic injury and is associated with sepsis syndrome.
Gamma E immunoglobulin (IgE) is associated with allergic reactions, but has not been described as being activated after trauma or sepsis. Total plasma IgE concentrations were determined in 32 patients with major traumatic injury, 29 patients undergoing elective abdominal operations, and 30 healthy volunteers. Mean total IgE concentrations were 271.7 ng/mL, 52.3 ng/mL, and 41.3 ng/mL, respectively (p less than 0.01 for each comparison with the trauma group). Total IgE concentrations in trauma patients at the time of admission were not significantly different from elective surgical controls, and tended to increase during the intensive care unit stay. In the trauma group, total IgE concentration was significantly greater in the 18 patients that developed sepsis syndrome compared with those that did not (p = 0.034). These data suggest that allergic mechanisms may be involved in the physiologic response to major traumatic injury and sepsis syndrome, or that other cells known to be involved in the immune responses to trauma and sepsis (macrophages, platelets, and B lymphocytes) may become activated by IgE-dependent mechanisms.
Prospective evaluation of the efficacy of technetium 99m sestamibi and iodine 123 radionuclide imaging of abnormal parathyroid glands.
BACKGROUND: Technetium 99m sestamibi is an isonitrile radionuclide imaging agent that, when used with subtraction iodine 123 thyroid scans, has the potential for imaging abnormal parathyroid glands. METHODS: We prospectively evaluated 20 patients with hyperparathyroidism to study the efficacy of Tc 99m sestamibi and 123I subtraction radionuclide scanning for the imaging of abnormal parathyroid glands. All patients underwent neck exploration and histologic confirmation of all parathyroid glands identified. RESULTS: The solitary adenomas in 11 of 16 patients with primary hyperparathyroidism were localized with sestamibi scans. The scans in four of five patients with diffuse parathyroid hyperplasia showed bilateral localization consistent with enlarged glands. The fifth patient previously underwent a subtotal parathyroidectomy, and a fifth supernumerary gland was localized with the sestamibi scan. Four patients had hyperparathyroidism related to kidney disease. Three of these had bilateral localization of enlarged glands. The fourth patient had undergone two previous operations, and a fifth supernumerary gland was localized with the sestamibi scan. CONCLUSIONS: The preliminary data indicate that Tc 99m sestamibi in combination with 123I radionuclide scanning may be useful in the preoperative localization of abnormal parathyroid glands. This technique localized all of the solitary adenomas that were subsequently resected, and in two reoperative cases it identified the remaining solitary gland causing persistent hypercalcemia.
Management of the injured renal transplant recipient.
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