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Biomedical subjects

J I Hirsch

Publications and source records attributed to J I Hirsch.

At least 37 records · Page 2Linked to original sources

Noninterference of isosulfan blue on estrogen-receptor activity.

Because a 1% sterile solution of methylene blue used for occult breast tumor localization has been shown to interfere with the estrogen-receptor protein (ERP) binding-capacity assay, isosulfan blue in a 1% injection was studied as a potential alternate stain. Cytosols derived from ERP-positive lyophilized powders and human breast tissue were evaluated with and without varying levels of treatment with isosulfan blue. No modification of the ERP-specific binding capacity was found with this stain. The use of isosulfan blue for localization of occult breast tumor is suggested when an ERP binding capacity assay is anticipated.

Biopsy, Needle↗

Reperfused-viable and reperfused-infarcted myocardium: differentiation with in vivo P-31 MR spectroscopy.

The ability of in vivo phosphorus-31 magnetic resonance (MR) spectroscopy to permit accurate distinction between reperfused-viable and reperfused-infarcted myocardium was examined in a canine model of acute coronary occlusion. In vivo myocardial pH and phosphocreatine, adenosine triphosphate, and inorganic phosphate levels were measured at baseline and for the first 90 minutes after reperfusion of a total coronary artery occlusion producing either predominantly viable (nine animals) or infarcted (nine animals) myocardium in the region of metabolic study. Myocardial viability was assessed in each animal by means of postmortem triphenyltetrazolium chloride staining. Tissue was characterized from the in vivo P-31 MR data by means of logistic regression analysis. The accuracy of using the P-31 MR data for distinguishing reperfused-viable from reperfused-infarcted myocardium was 100% (69 of 69 data points, 18 of 18 animals). Results of the logistic regression procedure indicated that phosphocreatine was the metabolic variable enabling most effective separation of reperfused-viable and reperfused-infarcted myocardium. Thus, metabolic data obtained with P-31 MR spectroscopy permit effective separation of reperfused-viable from reperfused-infarcted myocardium.

Adenosine Triphosphate↗

Preparation and evaluation of a 99mTc-SnF2 colloid kit for leukocyte labeling.

Stannous fluoride colloid (SFC) kits for instant radiolabeling with 99mTc were prepared and evaluated for suitability as a leukocyte radiolabeling agent. Technetium-99m labeling for kits stored at -15 degrees C for up to 3 mo was greater than 95% as determined by instant thin layer chromatography while colloid particles of 1-3 microns were measured by electron microscope for these preparations. Canine leukocyte preparations labeled with [99mTc]SFC and characterized by triple density gradients of metrizamide in plasma demonstrated an 83% leukocyte association. Analysis of labeled cell preparation for up to 3 hr demonstrated label stability. Labeled leukocytes, when readministered in normal dogs, demonstrated bi-exponential blood clearance with uptake and subsequent clearance from lung. There was increasing uptake of labeled leukocytes by the liver until steady state was achieved. Furthermore, when whole blood samples were analyzed by the triple density gradient method, an increasing monocyte-to-granulocyte ratio was observed to occur with time. By 3 hr 95% of the whole blood activity was associated with the leukocyte fraction. Dogs in which a 24-hr sterile abscess was created demonstrated elevated blood-pool activity as compared to control with localization of the labeled cells at inflammatory sites within 3 hr following cell readministration.

Abscess↗

Effective separation of normal, acutely ischemic, and reperfused myocardium with P-31 MR spectroscopy.

The ability of phosphorus-31 magnetic resonance (MR) spectroscopy to accurately characterize myocardium as normal, ischemic, or reperfused but viable was examined in the canine model of acute coronary artery occlusion. P-31 MR measurements of in vivo myocardial pH, phosphocreatine, adenosine triphosphate, and inorganic phosphate levels were made at baseline and for 6 hours after sustained coronary occlusion (ten animals) or coronary occlusion reperfused after 60 minutes (12 animals). Ten control animals were studied in parallel fashion, without coronary occlusion. Myocardial tissue characterization derived from the P-31 MR spectroscopy data by logistic regression analysis had an overall accuracy of 89%. Overall accuracy was unaffected by duration between coronary occlusion and P-31 MR study. Thus, metabolic data obtained with P-31 MR spectroscopy effectively separate normal, acutely ischemic, and reperfused but viable myocardium.

Adenosine Triphosphate↗

Effects of ibuprofen on a pig Pseudomonas ARDS model.

The effects of ibuprofen (I) were studied in the Pseudomonas (P) porcine ARDS model. Pigs, 14-26 kg (5 in each group), were anesthetized and ventilated with 0.5 FiO2 and 5 cm H2O PEEP. A control (C) group received saline only, a second group was given P, 1 X 10(8) org/ml at 0.3 cc/20 kg/min, and a third group was given P followed by 12.5 mg I at 20 and 120 min. Pulmonary arterial (PAP), wedge (PWP) and systemic arterial pressures, cardiac output (CO), and thermal-cardiogreen extravascular lung water (EVLW), thromboxane (TxB2), 6-keto-PGF1 alpha, PaO2, PaCO2 were determined every 30 min. Albumin flux was measured with scintigraphic determination of lung:heart radioactivity ratios versus time, called slope index (SI). At 3 hr, P produced marked (P less than 0.05) increases in PAP (18 +/- 7 to 37 +/- 2 mm Hg), TxB2 (471 +/- 513 to 9216 +/- 3615 pg/ml), 6-keto-PGF1 alpha, EVLW (6.4 +/- 1.4 to 14.6 +/- 5.7 mg/kg), and SI (0.4 +/- 0.2 to 1.7 +/- 0.5 X 10(-3) U/min) with decreases in PaO2 (214 +/- 47 to 101 +/- 41 torr), CO and SAP. Ibuprofen caused a rapid clearing of TxB2 and 6-keto-PGF1 alpha associated with a transient decrease in PAP; PaO2 was considerably improved compared to P; however, CO, SAP, EVLW, and SI were unaffected. Prostaglandin blockage temporarily ameliorated the pulmonary hypertension and markedly improved oxygenation in this porcine septic ARDS model, but failed to alter increased permeability, confirming other studies that the increased pulmonary shunt in ARDS is not only dependent upon capillary leak.

6-Ketoprostaglandin F1 alpha↗

Comparison of indium 111-labeled platelets v leukocytes in a pyogenic abscess.

This study sought to determine which blood component, WBCs or platelets, is the more specific indicator of an abscess and where each localizes. An abscess was created using stool in the hind limb of dogs. After 24 hours, one group was given autologous indium 111-labeled platelets and another group was given autologous indium 111-labeled WBCs. Blood, abscess fluid, infected operative control muscle tissue, and nonoperative control muscle tissue were counted for radioactivity 24 hours after administration of the labeled cells. There was significantly (P less than .001) less WBC radioactivity in blood and more within abscess fluid compared with platelets. The highest platelet activity occurred in muscle tissue adjacent to the abscess (P less than .002) compared with platelet activity in abscess fluid or control muscle tissue. The unwanted high platelet blood background activity and the desirable high concentration of WBC radioactivity within the abscess fluid makes the latter the preferential radionuclide imaging agent.

Abscess↗

Failure of methylprednisolone, ibuprofen, or prostacyclin to reduce HCl-induced pulmonary albumin leak in dogs.

The purpose of this study was to examine the effects of methylprednisolone (MP), ibuprofen (I), and prostacyclin (PGI2) pretreatment on cardiopulmonary hemodynamics, arterial oxygenation, and pulmonary alveolar-capillary membrane permeability, measured with a gamma-scintigraphic technique, after acid instillation in the dog. All animals were placed on their right side and 2 ml/kg 0.1 N HCl was instilled into the endotracheal tube. Five untreated control dogs showed a significant (p less than 0.05) rise in slope index (SI), a scintigraphic measurement of pulmonary albumin flux, 30 minutes after acid injury. After 120 minutes there was a significant rise in mean pulmonary arterial pressure (PAP) and pulmonary vascular resistance (PVR) and a decrease (p less than 0.05) in cardiac output (CO) and PaO2. Two groups of five dogs each were pretreated with MP (30 mg/kg) and I (12.5 mg/kg), respectively. Thirty minutes after acid instillation both groups showed a significant rise in the SI, which was significantly greater than the values in the control animals in the case of MP. By 120 minutes after acid injury all changes in PAP, PVR, PaO2, and CO were not significantly different from those of control animals with the exception of the I group, which resisted any change in CO throughout the study. Another group of five dogs were pretreated with a constant infusion of PGI2 (3 micrograms/kg/min) starting 75 minutes before acid instillation. PGI2 produced a significant increase in CO that was also greater (p less than 0.05) than the CO in control animals before instillation of HCl. Pre-HCl SI in the dogs treated with PGI2 was slightly, but significantly, increased over control dogs. The SI and CO remained significantly higher than values in control animals 30 minutes after acid injury. The SI remained significantly higher than that of control animals at 120 minutes. After 2 hours changes in PAP, PVR, PaO2, and CO were without significant difference from those of control animals. These data support the conclusion that PGI2, I, or MP are not effective therapy for acid aspiration and that PGI2 and I may worsen the protein leak by increasing flow across the damaged capillary membrane.

Albumins↗

Gamma scintigraphic localization of platelets labeled with indium 111 in a focus of infection.

To determine if autologous platelets would localize in a focus of infection, a pyogenic abscess was created in the left hind limb of dogs, using previously processed human stool, while an identical surgical procedure without bacterial inoculation was performed on the right hind limb. Autologous platelets labeled with indium 111 (500 microCi) were administered intravenously to five control dogs that had not undergone surgery, to eight dogs two hours following stool inoculation, and to five dogs 24 hours after stool inoculation. A statistically significant scintigraphic increase in tracer activity was apparent within 24 hours in each animal at the site of abscess creation. Tissue samples, obtained at 48 hours after the administration of labeled platelets, revealed a significant increase in percent dose of 111In per gram of infected muscle compared with control muscle. These studies show that platelets localize at the site of bacterial infection.

Abscess↗

Failure of various agents to decrease oleic acid pulmonary albumin leak.

Computerized pulmonary gamma scintigraphy has been shown to be a sensitive technique for the measurement of albumin flux in oleic acid pulmonary microvascular injury. In this technique technetium-99m-tagged human serum albumin is administered intravenously and lung:heart radioactivity ratios are constructed. This ratio remains constant unless there is a net flux of albumin from the vascular space into the lung, when a rising ratio is seen, called the "slope of injury" or SI. Gamma scintigraphy provides a method to rapidly screen the ability of various possible therapeutic agents to reduce the flux of albumin in experimental ARDS. In this study, 0.05 ml/kg oleic acid produced a significant increase in the SI. None of the agents tested (30 mg/kg methylprednisolone, 12.5 mg/kg ibuprofen, 4 mg/kg MK-447, a superoxide radical scavenger, or 140 mg/kg calcium gluconate) were able to alter the scintigraphically measured increased albumin flux produced by 0.05 ml/kg oleic acid.

Albumins↗

Pitfall to modified in vivo method of technetium-99m red blood cell labeling. Iodinated contrast media.

Suboptimal labeling of red blood cells with Tc-99m, using the modified in vivo technique, was observed in three patients in whom labeling was attempted following IV administration of iodinated contrast media in the previous 24 hours. The mechanism is not understood, but it may represent a change in either stannous ion distribution or redox potential. It is recommended that studies employing Tc-99m RBC labeling using this technique be performed prior to administration of iodinated contrast media. This effect should be kept in mind in gastrointestinal bleeding studies performed using Tc-99m RBC, as well as in cardiac imaging studies.

Child, Preschool↗

Comparative scintigraphy in oleic acid pulmonary microvascular injury.

Computerized gamma scintigraphy revealed a significant (p less than 0.001) rising lung:heart radioactivity ratio, which has been called "slope of injury" or "slope index", with both 99mTechnetium-tagged human serum albumin (99mTc-HSA) and 99mTechnetium-tagged red blood cells (99Tc-RBC) after 0.05 or 0.2 ml/kg iv oleic acid administration to dogs. This slope index was significantly greater with 99mTc-HSA than 99mTc-RBC (p less than 0.001). These findings verify that the scintigraphic 99mTc-HSA slope of injury is a result of a pulmonary capillary protein leak and not oleic acid induced changes in pulmonary blood or air volume. The leak of red blood cells noted with scintigraphy was confirmed by light microscopy and examination of the tracheal edema fluid. The leak of albumin, however, was much greater than the leak of red blood cells by microscopy and tracheal fluid examination, confirming the scintigraphic data. This study provides further evidence that computerized gamma scintigraphy will be of value for the diagnosis of permeability pulmonary edema and its response to treatment.

Animals↗

Scintigraphy and radiography in oleic acid pulmonary microvascular injury: effects of positive end-expiratory pressure (PEEP).

Using computerized gamma scintigraphy, 10-cm H2O PEEP did not alter the rate of capillary protein leakage in dogs following pulmonary microvascular injury with 0.01 to 0.2 ml/kg oleic acid. A rising lung:heart radioactivity ratio, or 'slope of injury,' was seen during PEEP which paralleled the 'slope of injury' had PEEP not been used. A sudden decrease in lung and heart count activity (p less than 0.001) and decreased lung:heart radioactivity ratio (p less than 0.001) occurred with PEEP at all doses of oleic acid studied. An apparent improvement in the standard chest roentgenogram was seen within 2 minutes following PEEP in dogs given 0.2 ml/kg oleic acid. However, progression of the radiographic infiltrate occurred in these animals during 30 minutes of PEEP. When all vessels leading to and from the heart and lungs were ligated, PEEP produced a 60% fall in count activity over the lung without any change in cardiac radioactivity. The apparent radiographic improvement and 2/3 of the fall in lung radioactivity with PEEP were due to an increased pulmonary air volume and 1/3 due to a decreased pulmonary blood volume. The decreased cardiac output with PEEP must be secondary to decreased ventricular filling rather than decreased ventricular function.

Animals↗

Computerized scintigraphic technique for the evaluation of adult respiratory distress syndrome: initial clinical trials.

Eleven patients with suspected adult respiratory distress syndrome (ARDS) and five control patients were studied using a computerized gamma imaging and analysis technique and 99mTc-labeled human serum albumin. The heart and right lung were imaged, lung:heart ratio was plotted vs. time, and a linear regression was fitted to the data points displayed. The slope of this fit was termed the "slope index." An index value of 2 standard deviations greater than the control mean was considered positive. Radiographs from the six positive studies revealed typical diffuse air-space disease. Radiographs from two of the five negative studies demonstrated air-space consolidation. Both of these patients had elevated pulmonary capillary wedge pressure, cardiomegaly, and clinical course consistent with cardiogenic pulmonary edema. These preliminary data demonstrated a good correlation between positive slope index and clinical ARDS.

Adult↗

Use of isosulfan blue for identification of lymphatic vessels: experimental and clinical evaluation.

Use of vital dyes for identification of lymphatic vessels before cannulation has heretofore not been approved by the Food and Drug Administration (FDA). The suitability of isosulfan blue, the 2,5 disulfonic acid isomer of Patent Blue, for this purpose was evaluated experimentally in the rat and clinically in 11 volunteers and 543 patients under an investigational new drug application. FDA approval for this drug has been obtained. Volunteers and patients received up to 15 mg of a 1% sterile, pyrogen-free solution per extremity (total dose of 0.4 mg/kg in the average patient). Excellent identification of lymphatic vessels was achieved in 100% of volunteers and in 97.4% of patients. In the other 2.6%, lymphatic vessels were not identified mainly due to congenital lymphatic vascular (Milroy) disease. Baseline blood chemistry in volunteers was not altered after administration of the dye. No adverse reactions were found in volunteers and minimal allergic reactions occurred in less than 1% of patients. Acute toxicity studies demonstrated an LD50 greater than 150 mg/kg in the rat. Isosulfan blue was excreted unchanged in the urine (7%) and feces. Comparable excretion was found in volunteers. Isosulfan blue is a safe and efficacious vital dye for lymphangiography.

Adult↗

Sensitivity of scintigraphy for detection of pulmonary capillary albumin leak in canine oleic acid ARDS.

Computerized gamma scintigraphy was shown in this study to be a sensitive technique for the detection and kinetic analysis of a pulmonary capillary protein leak. A rising lung:heart radioactivity of 'slope of injury' was found at each dose of intravenous oleic acid in dogs from 0.01 to 0.20 ml/kg (p less than 0.01). This 'slope of injury' was proportional to the dose of oleic acid (r = +0.97; p less than 0.004) and was more sensitive than changes in arterial oxygen tension, standard chest radiography, bloodless wet:dry lung weight, or alveolar epithelial membrane permeability. Only standard light microscopy and right lymphatic duct flow were able to document the leakage of protein detected by gamma scintigraphy at 0.01 ml/kg oleic acid.

Albumins↗