Sezary syndrome.

Sezary syndrome is a rare form of primary cutaneous T cell lymphoma. A male patient of 37 years old was reported with multiple subcutaneous swelling at different parts of the body which were asymptomatic for the last 2 years. But he had persistent generalized itching, induration in skin surface and erythema for months. The disease was diagnosed by the presence of Sezary cells in the skin biopsy, peripheral blood smears and epidermotrophism of lymphocytes. The patient was treated by CHOP (Cyclophosphamide, Doxorubicin, Vincristine and Prednisolone) therapy.

Intravascular contrast media and thrombin generation.

This study focuses on the effect of contrast media (CM) on thrombin generation. In vitro studies consisted of incubating nonanticoagulated whole blood with ionic CM (sodium meglumine diatrizoate, ioxaglate), nonionic CM (iohexol, iopamidol) or glucose in plastic tubes. Thrombin generation was assessed by measuring F1 + 2, ATM and FpA levels in plasma using ELISA assay kits. In a separate protocol, the procoagulant activity of 3 nonionic CM (iohexol, iopamidol, and iopromide) was investigated by one-stage plasma recalcification time method. Rabbit brain tissue thromboplastin and physiologic saline were used as standard and experimental controls. Incubation of ionic and nonionic CM with whole blood did not enhance thrombin generation compared to glucose control. Similarly, the plasma recalcification times were not significantly shortened by either of the 3 nonionic CM tested. These studies suggest that ionic and nonionic CM exhibit different levels of anticoagulant properties in vitro and the latter are not procoagulant materials.

Ultrasonic surgical aspirator for lung resection.

The ultrasonic surgical aspirator was originally developed for neurosurgical procedures and hepatic resections. Ultrasonic vibration at the tip of the instrument results in lysis of the parenchymal cells, leaving more resistant fibrous tissue such as blood vessels and bronchi intact and, thus, minimizing blood loss. We have studied the feasibility of applying the ultrasonic surgical aspirator for segmental and subsegmental lung resection for primary and metastatic neoplasms of the lung. Over the past 5 years, 27 patients underwent segmental or limited lung resection using the ultrasonic surgical aspirator. Except for prolonged air leak in 6 patients postoperatively, no other serious morbidity was noted. We observed several advantages: (1) the ultrasonic surgical aspirator dissects out the pulmonary vessels and bronchi, allowing the surgeon to perform segmental and subsegmental resections with minimal blood loss, (2) it permits lung-sparing operation for centrally located tumors that would otherwise have required lobectomy, and (3) it allows direct visualization of lung parenchyma during dissection, thus assuring grossly adequate margins.

Adrenalectomy for adrenal metastasis from lung carcinoma.

In the past 3 years, five patients with lung carcinoma were found to have enlarged adrenal glands without any evidence of distant metastasis. The patients were treated with adrenalectomy. The cases are presented in order to discuss optimal methods of diagnosis and treatment for this condition.

Contrast media-induced lipid peroxidation in the rat kidney.

Lipid peroxidation of biological membranes is often implicated in tissue injury. The authors compared the effects of ionic and nonionic contrast media (CM) on the induction of lipid peroxidation in rat kidney and its impact on renal function. Male Wistar rats weighing 200 to 230 grams were dehydrated for 24 hours and divided into 6 groups (n = 15/group). On day 0, groups 1 through 3 were injected with 25% glycerol (10 mL/kg, im) and rats from groups 4 through 6 received an equivalent amount of intramuscular saline. The next day, rats from groups 1 and 4 were injected with normal saline (10 mL/kg, iv); groups 2 and 5 received the ionic CM, diatrizoate, and groups 3 and 6 received the nonionic CM, iopromide. Each CM was tested at 10 mL/kg BW. At 24-hour intervals, 5 rats from each group were sacrificed. In rats injected with CM (diatrizoate or iopromide) alone, no changes in serum creatinine or kidney structure were demonstrated. In glycerol treated rats, a peak in serum creatinine was seen on day 2 which returned to normal level by day 4. Histologic changes included focal tubular damage and intraluminal debris. Malondialdehyde (MDA), a marker of lipid peroxidation concentration was higher than in controls (P less than 0.05). In diatrizoate-injected rats, increase in serum creatinine on day 4 was ten times higher than glycerol; severe morphological alterations in proximal tubules were noted and significant increases in renal MDA concentration were obtained (P less than .05). Iopromide (on day 4), caused a five-fold increase in serum creatinine compared with glycerol.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of a new nonionic contrast agent, ioxilan, on human erythrocytes and the hemostatic and serum complement pathways.

A new nonionic contrast medium (CM), ioxilan, was compared with iohexol and iopamidol. Following incubation of whole heparinized blood with CM, the morphology and osmotic fragility of erythrocytes were studied, the former by transmission electron microscopy. Effects on platelets and hemocoagulation were determined by standard hematologic procedures. Effects on serum complement were evaluated by measurement of total hemolytic complement (CH50), C3, C4 consumption and the presence in serums of C3c as determined by immunoelectrophoresis. Ioxilan affected the erythrocyte membrane less than iohexol and iopamidol: the latter two produced acanthocytes, whereas ioxilan had no effect on erythrocyte morphology; also, erythrocytes exposed to ioxilan (and iopamidol) were more resilient to hypotonic saline solutions than those exposed to iohexol. In all tests, all CM showed anticoagulant activity, albeit much less when compared with ionic CM. At equal iodine concentration, ioxilan reduced the platelet aggregation and whole blood clotting time more than did iohexol. None of the CM activated the serum complement system.

Effect of contrast media on prostaglandin synthesis in vivo.

Since systemic reactions to contrast media (CM) in patients often resemble pathophysiologic conditions associated with prostaglandin metabolites prostacyclin (PGI2), and thromboxane B2 (TXB2), plasma levels of these mediators are likely to provide an index of CM pathogenesis. In this study, patients undergoing peripheral arteriography were injected either with a hyperosmolal CM sodium diatrizoate or with a newer low osmolal CM, iohexol. Arterial blood samples were collected before and after the procedure. Prostacyclin and thromboxane were quantified as 6 ketoprostaglandin F1a (PGF1a) and TXB2 by using radioimmunoassay kits. Diatrizoate caused prostaglandin I2 (PGI2) release in 60% of patients, whereas 66% receiving iohexol also exhibited increased levels of PGI2 in their plasma. TXB2 concentration remained unchanged. No clinically adverse reactions were seen following the procedure. These results indicate that both high and low osmolality CM are capable of stimulating vascular endothelium, thereby causing prostacyclin release. Molecular mechanisms, however, remain to be determined.

Cytogenetic interactions of contrast media and antineoplastic drugs.

The cytogenetic interactions of ionic (diatrizoate, ioxaglate) and nonionic (iohexol) contrast media (CM) with antineoplastic drugs cyclophosphamide (CPA) and carmustine (CARM) were evaluated in a rat bone marrow cell model. Male Wistar rats were anesthetized with a 6% chloral hydrate solution and divided into five groups of five rats each. In protocol 1, three groups of rats received diatrizoate, ioxaglate, and iohexol (2.5 mL/kg) intravenously within 30 seconds. The remaining two groups were similarly injected with CPA and CARM (10 mg/kg). Control animals were injected with nonpyrogenic sterile water or saline solution. After 12 and 24 hours, the animals were killed with an overdose of chloral hydrate, and bone marrow smears were prepared for determining chromosomal damage in polychromatic erythrocytes (PCEs) by a micronucleus test. In protocol 2, CPA and CARM were injected, and 15 minutes later, bolus injections of diatrizoate, ioxaglate and iohexol were given through the same route. Both ionic and nonionic CM induced significant numbers of micronuclei in PCEs (P less than .05). CPA caused a severe cytogenetic effect, whereas CARM did not produce a significant number of micronuclei in PCEs compared with control. In protocol 2 experiments, antagonism with CPA and synergism with CARM was demonstrable. Clinical implication of the cytogenetic interactions between CM and antineoplastic drugs remains to be established.

Induction of mitotic micronuclei by X-ray contrast media in human peripheral lymphocytes.

In vitro and in vivo cytogenetic effects of X-ray contrast media (CM) were determined by scoring micronuclei (MN) in 72-h cultures of human peripheral lymphocytes. Both ionic (sodium meglumine diatrizoate, methylglucamine diatrizoate, and sodium meglumine ioxaglate and nonionic CM (iosimide, iopromide, iohexol and iotrolan) were able to induce MN in lymphocytes. Based upon their calculated percent probabilities for MN induction, these agents could be ranked in their decreasing order of probability, as iosimide greater than sodium meglumine ioxaglate greater than iohexol greater than sodium meglumine diatrizoate greater than iopromide greater than methylglucamine diatrizoate greater than iotrolan. Stepwise logistic regression analysis of the data indicated that the frequency of MN in CM-exposed lymphocyte cultures was significantly higher than the frequency of MN in control cultures (P less than 0.001). In clinical studies where 14 patients were injected with an ionic CM methylglucamine diatrizoate, lymphocyte cultures from 10 patients showed higher frequencies of MN. The differences between pre- and post-CM counts of MN were significant in a Mann-Whitney U test (P less than 0.05). The effect of X-irradiation on MN formation in lymphocytes was separately determined and was found to be insignificant. These results indicate that irrespective of ionic and osmolality differences, X-ray contrast agents are capable of producing chromosomal damage in peripheral lymphocytes. Further studies are required to establish molecular mechanisms in the observed cytogenetic effects of CM in cell cultures.

Contrast media-induced chromosomal damage in human lymphocyte cultures.

Ionic (diatrizoate, ioxaglate) and nonionic (iohexol, iosimide, iopromide, and iotrolan) contrast media (CM) were evaluated for their cytogenetic effects in lymphocytes. Heparinized blood was mixed with culture medium RPMI-1640 supplemented with phytohemagglutinin, fetal calf serum, and antibiotics. Plastic tubes containing blood samples were incubated at 37 degrees C in 5% CO2 humidified air for 48 hours. To these cultures, increasing amounts of CM were added and cells incubated for an additional 24 hours. After this exposure, red blood cells were lysed with hypotonic KC1, lymphocyte smears fixed on glass slides and stained with May-Grünwald Giemsa. Chromosomal damage was analyzed by a micronucleus test. All CM tested induced micronuclei in lymphocytes quite significantly (P less than .001) when compared with the frequency of micronuclei in controls. These observations on the genotoxic potential of nonionic CM suggest that factors other than ionic composition and osmolality are involved in clastogenesis; further studies are needed to establish the molecular mechanisms in CM induced chromosomal damage.

Nonionic contrast medium: effects on blood coagulation and complement activation in vitro.

A nonionic contrast medium was evaluated in vitro for its effects on coagulation and complement activation in comparison to a low osmolal contrast agent. In clotting assays each contrast medium was mixed with blood and clotting parameters were analyzed by using a thromboelastographic machine. Platelet function was studied by incubating platelet-rich plasma with individual contrast medium, and the subsequent challenge of a platelet aggregating agent. Complement activation was assessed by the hydrolysis of C3 protein into C3c fragment in contrast medium-incubated serum. Immunoelectrophoresis was used to detect C3c protein. Both the nonionic contrast medium and the low osmolal contrast agent acted as anticoagulant and antiplatelet agents, however, results with the low osmolal contrast agent were more pronounced compared to the nonionic contrast medium. Even at nonphysiologic concentration of contrast medium, no significant conversion at C3 to C3c was seen. Since these two agents caused hypocoagulable states in vitro, it is likely that patients with thrombocytopenia, severe liver disease and with clotting factor deficiencies may present hemostatic complications during angiographic procedures.

Ultrastructural changes in rat aortic endothelium during contrast media infusion.

A rat model was employed to investigate contrast media (CM) induced ultrastructural changes in the vascular endothelium. Ionic contrast materials such as Renografin-76 (diatrizoate meglumine diatrizoate sodium), MD-76 (diatrizoate meglumine diatrizoate sodium), and Angiovist (meglumine diatrizoate) were injected into the femoral vein of anesthetized male Wistar rats (240-260 g) and allowed to circulate. Control animals were similarly injected with equiosmolar sucrose and physiologic saline. The thorax was opened 15 minutes, 1 hour, and 4 hours postinjection and cardiac perfusion performed using Karnovsky's fixative; the thoracic aorta was then surgically removed, and processed for transmission electron microscopy. All CM produced shrinkage in cell cytoplasm and nuclear structures thereby causing distortions in cell morphology. In control tissues, however, no such ultrastructural damages were noted. Within 15 minutes of CM infusion, electron dense granules were seen on the luminal surface of endothelial cells, in pinocytotic vesicles, as well as in the gap junctions between cells. These observations indicate that contrast media intake occurs via vesicular transport, and through the cell junction.

Complement abnormalities during contrast media procedures.

Complement changes following the administration of the two most commonly used intravascular contrast media (CM) diatrizoate and iothalmate were studied in 26 patients by measuring complement component C3 levels and the total hemolytic function. Blood from these patients was obtained in plastic tubes containing 10 mM ethylene diamine tetra-acetic acid (EDTA) prior to and 15 min after contrast media infusion. In thirteen patients who received iothalamate a 28% drop in C3 concentration and a 19% change in total hemolytic complement was seen. In the second group of thirteen patients diatrizoate caused a 20% C3 decrease and a 15% reduction in total hemolytic complement. Since iothalamate is a hyperosmolar and hyperviscous solution compared to diatrizoate, it is likely that these factors are responsible for changes in complement level which may present potential risk to patients with depressed immunologic status. This study suggests that screening of patients for their total complement profile may provide useful information in minimizing adverse reactions to contrast material.

Antiplatelet action of intravascular contrast media. Implications in diagnostic procedures.

The antiplatelet action of intravascular contrast media (CM) Renografin-76 (diatrizoate meglumine and diatrizoate sodium) was studied in vitro and in 21 patients undergoing radiodiagnostic procedures. In vitro studies suggested that in Renografin-76, meglumine was the chief constituent responsible for its antiplatelet action. In post-CM plasma from patients, clotting times were prolonged and platelet aggregation greatly impaired, albeit normal aggregation restored within 3 hours. Although changes in global clotting times and platelet aggregation were mostly transient, it is possible that CM usage in patients with thrombocytopenia, sickle cell phenomenon, and on anticoagulant-antiplatelet drugs may present a serious risk to their hemostatic integrity.