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Biomedical subjects

D Zuckerman

Publications and source records attributed to D Zuckerman.

17 recordsLinked to original sources
PubMed1996

Buffy coat platelets stored in apyrase, aprotinin, and ascorbic acid in a suspended bag: combined strategies for reducing platelet activation during storage.

BACKGROUND: Platelet activation is an important factor impeding the clinical effectiveness of platelet transfusions. In this study, platelet concentrates (PCs) were prepared by a novel suspended-bag buffy coat technique that was followed by the addition of a mixture of platelet activation inhibitors to the storage bag. STUDY DESIGN AND METHODS: In vitro platelet function was evaluated in PCs prepared by the suspended-bag buffy coat technique and stored at 22 degrees C for 5 days in the presence of (n = 12) or absence (n = 12) of apyrase, ascorbic acid, and aprotinin (AAA). RESULTS: Platelets from AAA-incubated PCs demonstrated mean ATP levels 17 percent (p < 0.004), 13 percent (p < 0.02), and 22 percent (p < 0.003) higher than those measured in parallel control PCs on Days 1, 3, and 5, respectively. Similarly, on Days 3 and 5 of storage, respectively, 45-percent (p < 0.001) and 50-percent (p < 0.001) greater ADP-induced maximum aggregation was observed in AAA-incubated PCs than was seen in control preparations. AAA-incubated PCs demonstrated alpha-granule membrane protein-140 expression 92 percent (p < 0.01), 133 percent (p < 0.003), and 104 percent (p < 0.001) below that in control PCs on Days 1, 3, and 5, respectively. At similar intervals, a significant increase in recovery from hypotonic shock also was observed in AAA-incubated PCs. Further, Day 5 AAA-PCs demonstrated significantly higher morphology scores and O2 consumption than did control preparations. CONCLUSION: Buffy coat platelets prepared in suspended bags and stored in the presence of AAA demonstrate significantly reduced activation and enhanced functional and metabolic activity.

Aprotinin↗
PubMed1994

Effects of interleukin-2 administration on platelet function in cancer patients.

Platelet function in 16 patients with metastatic renal cell carcinoma and melanoma was studied sequentially over the first 96 hr of treatment with moderate and high-dose interleukin-2 (IL-2). During the first 96 hr of therapy, an increased ex vivo platelet maximal aggregation (MA) response to ADP, epinephrine, and arachidonic acid was paralleled by a decrease in the peripheral platelet count. Plasma specimens from patients receiving the moderate dose schedule showed a significant IL-2 induced secretory response of the platelet alpha-granule components beta-thromboglobulin (BTG) and platelet factor 4 (PF4) and the eicosanoid thromboxane B2 (TBX2) as measured by RIA. The increase in TXB2 was highly correlated with MA when analyzed by bivariate regression analysis, whereas the addition of PF4 to TXB2 in a multiple regression analysis further increased their correlation to MA. The observed decrease in peripheral platelet count correlated significantly with MA and PF4 secretion. High-dose IL-2-treated patients showed a statistically significant increase in the percentage of large platelets exceeding 12 fl in diameter and platelet responsiveness to hypotonic shock. These observations suggest that IL-2 therapy results in a reduced peripheral platelet pool, with an increased proportion of the remaining pool of platelets larger, more viable, and activated.

Adult↗
PubMed1994

Computed tomography in the diagnosis of blunt thoracic injury.

BACKGROUND: Computed tomography (CT) is an important diagnostic modality in the evaluation of blunt head and abdominal injuries, but it has not been routinely used to evaluate blunt chest trauma. METHODS: One hundred seventy stable patients with blunt thoracic trauma were evaluated with chest x-ray (CXR), and subsequently by CT. RESULTS: Of a total of 131 fractures, 53% were identified on initial CXR, 39% on CT, and 26% were not seen on either study. Twenty-one pneumothoraces were seen on CT but not on CXR. Chest tubes were placed in 8 patients and 12 patients were observed without incident. One hemothorax identified by CT scan alone required treatment. Four of 6 diaphragmatic injuries were seen on CT and 2 on CXR. Parenchymal abnormalities were apparent in 189 lung fields on CT and in 66 lung fields on CXR. Most represented atelectasis and did not require treatment. Altogether, CT scanning resulted in changes in management for 11 patients (6%). CONCLUSIONS: Although CXR is less sensitive in detecting parenchymal and pleural injuries than CT, the majority of the injuries identified by CT alone are minor and require no treatment. CXR remains the primary modality for diagnostic evaluation of blunt thoracic trauma.

Adult↗
PubMed1994

Computed tomography as a screening exam in patients with suspected blunt aortic injury.

BACKGROUND: Chest computed tomography (CT) screening of patients with blunt trauma for thoracic aortic injury is controversial. This study was undertaken to determine whether CT could exclude aortic injury and be used to select patients for aortography. METHODS: Computed tomography and aortography were used to evaluate 155 patients with blunt trauma. Computed tomography scans were reviewed separately by four attending radiologists who were unaware of the patients' clinical course and angiographic findings. RESULTS: Eight of 155 patients had aortic injuries requiring operation. Computed tomography scans in five patients were read as positive by all reviewers. One scan was read as positive by three reviewers and as negative by one. Two scans were read as positive by two radiologists and as negative by two. After poor scans were excluded, the combined sensitivity of CT for detecting aortic injury was 88%, specificity was 54%, positive predictive value was 9%, and negative predictive value 99%. CONCLUSIONS: The sensitivity of CT scan for indicating the need for aortography is observer dependent. As CT manifestations of aortic injury are often subtle, CT does not reliably exclude aortic injury.

Adolescent↗
PubMed1994

Analysis of radiocontrast-induced nephropathy by dual-labeled radionuclide clearance.

RATIONALE AND OBJECTIVES: This study was devised to develop a method of measuring the acute effects of radiocontrast media on renal function and assessing the relationship of the dose of radiocontrast media infused with the incidence of radiocontrast-induced renal failure. In addition, the drug adenosine phosphate-magnesium chloride (ATP-MgCl2) was evaluated as a renoprotective agent. METHODS: Eighteen patients with pre-existing renal impairment, (serum creatinine greater than 133 mumol/L) were randomized to receive a continuous infusion of ATP-MgCl2 or placebo before and during a radiocontrast procedure. Subjects were monitored with daily serum creatinine and with radionuclide renal clearance studies at baseline, during, and 24 hours after the radiocontrast procedure. RESULTS: There was an initial deterioration in renal clearance in the entire study group (from 44.2 +/- 4.6 to 32.6 +/- 3.9 mL/min, P = .001) which was independent of the dose of radiocontrast infused. There was a persistent deterioration in renal clearance only in those who received greater than 135 mL of contrast media (from 48.6 +/- 7.8 to 37.1 +/- 3.9 mL/min, P = .05). There also was an increase in serum creatinine that persisted only in those subjects who received greater than 135 mL of contrast media (230 +/- 27 to 283 +/- 44 mumol/L, P = .01). CONCLUSION: Persistent deterioration in renal function after radiocontrast administration appears to be dose-dependent and is not prevented by the use of ATP-MgCl2. Radionuclide techniques are useful in monitoring acute changes in renal function during radiocontrast procedures and may be of value in assessing renal impairment in future intervention studies.

Acute Kidney Injury↗
PubMed1994

Platelet activation induced by interleukin-6: evidence for a mechanism involving arachidonic acid metabolism.

The effect of IL-6 on in vitro platelet function was investigated. Platelet-rich plasma (PRP) incubated with IL-6 showed a dose dependent enhancement of agonist induced maximum aggregation (AIMA) and secretion of thromboxane B2 (TXB2) as measured by RIA, in short term incubations. Dazoxiben (0.2 to 160 microM) pretreated PRP incubated with IL-6 and aggregated with ionophore A23187, showed a dose dependent inhibition of TXB2 secretion concomitant with a dose dependent abrogation of IL-6's enhancement of AIMA. A similar abrogation of AIMA was observed when these experiments were repeated using indomethacin. Further, PRP incubated with IL-6 showed a dose dependent increase in TXB2 and BTG secretion as measured by RIA and an increased incorporation of actin binding protein, talin, and myosin into the cytoskeletal core (triton insoluble residue) as shown by SDS-PAGE. The integrin glycoprotein IIIa (GPIIIa) was also observed to be retained into the cytoskeleton by immunoblot. These results suggest that IL-6 activates platelets in vitro and enhances AIMA via a mechanism involving arachidonic acid metabolism.

Adenosine Diphosphate↗
PubMed1993

Role of interleukin-2 and mononuclear cells in platelet-tumor interactions.

Interleukin-2 (IL-2) has been reported to induce mononuclear cell-dependent platelet perturbations and to reduce the incidence of metastases in rodent models. In this study, MC-1 leukemic cell-induced platelet aggregation was associated with a significant increase in thromboxane B2 (TXB2) secretion, quantified by RIA, but a decrease in leukotriene B4 (LTB-4) secretion compared to incubations of tumor cells alone. Whereas MC-1 cells also activated platelets as observed by a significant increase in scanning electron-microscopic spheroidal forms distributed throughout the platelet pool, increasing concentrations of IL-2-activated peripheral blood mononuclear cells (PBMC), but not IL-2 or PBMC alone, reversed this effect with a reduction in activated spheroidal forms. The addition of IL-2-activated PBMC to MC-1 platelet incubations inhibited platelet-tumor cell adhesion and suppressed MC-1-induced aggregation. In order to investigate the mechanism resulting in inhibition of MC-1-induced platelet aggregation, short-term PRP-MC-1 preparations were incubated with IL-2-activated PBMC and assayed for TXB2 and LTB-4 by RIA. LTB-4 levels were significantly elevated in these preparations while levels of TXB2 were significantly reduced compared with control platelet-rich plasma (PRP)-MC-1 incubations. Our results showed that inhibition of MC-1-induced platelet activation, aggregation and tumor-platelet adhesion by the addition of IL-2-activated PBMC was consequent to a cellular effect of IL-2 on PBMC. These findings may be important in understanding the observed antimetastatic effect of IL-2.

Adult↗
PubMed1991

Alterations of platelet function induced by interleukin-2.

We recently reported that thrombocytopenia and bleeding are often limiting effects of immunotherapy with interleukin-2 (IL-2). In order to understand the mechanisms that lead to this unexpected clinical toxicity, we studied the effects of IL-2 on in vitro platelet function. When platelet aggregation was studied using whole blood (impedance, electrical) aggregometry, inhibition of aggregation was detected within 1 min of the addition of exogenous IL-2 to whole blood. IL-2-induced platelet secretion was quantified by radioimmunoassay (RIA) of PF4, BTG, and TXB2 independent of the addition of an aggregating agonist (ADP). Platelet secretion and inhibition of aggregation were an indirect consequence of a cellular effect of IL-2 on mononuclear cells, since aggregation was normal when whole blood was depleted of mononuclear cells and its reconstitution with autologous mononuclear cells led to a cell concentration-dependent inhibitory effect of aggregation and release of alpha-granule components in the presence of IL-2. In order to understand the mechanism of platelet secretion mediated by IL-2-activated mononuclear cells, we quantified the release of eicosanoid products from cultures of mononuclear cells exposed to IL-2 and found a significant increase in TXB2. Our results indicate that platelet secretion, indirectly initiated by IL-2-activated cells, is followed by inhibition of aggregation. These findings may not only have important implications for the planning of clinical immunotherapy trials with IL-2, but may also provide a novel link for a better understanding of the relationships between the hemostatic and the immune systems.

Blood Platelets↗
PubMed1984

Use of personal computing technology by deaf-blind individuals.

This paper describes a system that enables deaf-blind people to work with microcomputers. The system utilizes the International Morse Code as a general communication medium. The deaf-blind person "hears" Morse code via a vibrotactile device to "see" the computer's screen. This technique enables deaf-blind individuals to receive immediate feedback from their typing and to scan the screen. This makes it possible for them to use the keyboard and screen in the same way as do seeing persons. A side benefit is that it provides a means for deaf-blind people to communicate with the sighted through a common medium. The sighted person can see the screen while the deaf-blind person feels it. Hardware cost to equip a standard personal computer with this interface is negligible. Vibrotactile Morse code is particularly viable because it can be adapted for the individual's particular tactile sensitivities. Morse-encoded tactile communication fits well in a social facilitation context for learning. It is technologically simple and standard. This work can significantly improve the quality of life for deaf-blind individuals because it provides new opportunities for communication and vocation.

Blindness↗