A chemically induced rat model of hemolysis with disseminated thrombosis

Although hemolytic anemia and thrombosis, which can be serious or even lethal, are often encountered in daily common practice., their pathogenesis has remained obscure, partially because of the absence of appropriate models. Here we present a unique chemically induced rat model of hemolytic anemia and disseminated thrombosis in which the organs developing infarction are comparable to those seen in humans. We exposed male and female Fischer F344 rats to two, three, or four daily doses of 2-butoxyethanol (BE) at 250 mg/kg body weight and examined for hemolysis and histopathological evidence of disseminated thrombosis on d 2, 3, 4, and 29. Time-course BE-related erythrocytic changes were statistically significant in both sexes. Evidence of thrombosis and infarction was seen mainly in females dosed more than once with widespread thrombotic crisis after two or three dosings, likely explicable by the more significant morphological changes in erythrocytes and hemolysis observed in this gender. We documented thrombosis and infarction in the heart, brain, Jungs, eyes, and bones. Our model with its list of target organs similar to that observed in human diseases characterized by hemolysis and thrombosis [for example, thalassemia, sickle cell disease (SCD), paroxysmal nocturnal hemoglobinuria (PNF), disseminated intravascular coagulation (DIC), thrombotic thrombocytopenic purpura (TTP), and hemolytic uremic syndrome (HUS)] suggests that it can be an excellent tool to study the pathogenesis of such complications. This investigation is dedicated to the memory of Professor Amiram Eldor.     

Surgical resection of pulmonary metastases from colorectal adenocarcinoma

From 1962 to 1982, 27 patients with pulmonary metastases as the only site of recurrent colorectal carcinoma underwent pulmonary resection at Roswell Park Memorial Institute. Only five of these patients had symptomatic pulmonary lesions. No postoperative mortality occurred. The median survival after pulmonary resection was 27 months. Five patients are alive presently without recurrent colorectal cancer and two patients are alive with recurrent pulmonary metastases. Patients with solitary lesions had a better survival than patients with multiple lesions. The major sites of recurrence following thoracotomy were the lungs and liver. Junior Faculty American Cancer Society. Aided by grant JFCF 773 from the American Cancer Society.     

Treatment of Resistant Thrombotic Thrombocytopenic Purpura with Rituximab and Cyclophosphamide

Thrombotic thrombocytopenic purpura (TTP) is an uncommon acquired disease in adults, especially young women, characterized by fever, neurologic manifestations, microangiopathic hemolytic anemia, thrombocytopenia, and renal dysfunction. Treatment with plasmapheresis has increased the survival rate from 10% to greater than 90%. Still, a subset of patients with resistant TTP fail to respond to plasmapheresis or remain dependent on this procedure. We report such a patient who was successfully treated with rituximab and cyclophosphamide. She has now been disease free for more than 6 months. This novel treatment modality for TTP has been described for only a few patients. A well-controlled clinical trial is warranted to determine the role and place of this therapeutic approach in the management of TTP.     

The faster potassium-lowering effect of high dialysate bicarbonate concentrations in chronic haemodialysis patients.

BACKGROUND: Hyperkalaemia is common in patients with advanced renal disease. In this double-blind, randomized, three-sequence, crossover study, we compared the effect of three dialysate bicarbonate concentrations ([HCO3-]) on the kinetics of serum potassium (K+) reduction during a conventional haemodialysis (HD) session in chronic HD patients. METHODS: We studied eight stable HD patients. The choice of dialysate [HCO3-] followed a previously assigned treatment protocol and the [HCO3-] used were low bicarbonate (LB; 27 mmol/l), standard bicarbonate (SB; 35 mmol/l) and high bicarbonate (HB; 39 mmol/l). Polysulphone dialysers and automated machines provided blood flow rates of 300 ml/min and dialysis flow rates of 500 ml/min for each HD session. Blood samples were drawn at 0 (baseline), 15, 30, 60 and 240 min from the arterial extracorporeal line to assess blood gases and serum electrolytes. In three of the eight patients, we measured serum K+ 1 h post-dialysis as well as K+ removal by the dialysis. The same procedures were followed until the completion of the three arms of the study, with a 1 week interval between each experimental arm. RESULTS: Serum K+ decreased from 5.4+/-0.26 (baseline) to 4.96+/-0.20, 4.90+/-0.19, 4.68+/-0.13 and 4.24+/-0.15 mmol/l at 15, 30, 60 and 240 min, respectively, with LB; from 5.38+/-0.21 to 5.01+/-0.23, 4.70+/-0.25, 4.3+/-0.15 and 3.8+/-0.19 mmol/l, respectively, with SB; and from 5.45+/-0.25 to 4.79+/-0.17, 4.48+/-0.17, 3.86+/-0.16 and 3.34+/-0.11 mmol/l, respectively, with HB (P<0.05 for high vs standard and low [HCO3-] at 60 and 240 min). The decrease in serum K+ correlated with the rise in serum [HCO3-] in all but LB (P<0.05). Potassium rebound was 3.9+/-10.2%, 5.2+/-6.6% and 8.9+/-4.9% for LB, SB and HB dialysates, respectively (P=NS), while total K+ removal (mmol/dialysis) was 116.4+/-21.6 for LB, 73.2+/-12.8 for SB and 80.9+/-15.4 for HB (P=NS). CONCLUSIONS: High dialysate [HCO3-] was associated with a faster decrease in serum K+. Our results strongly suggest that this reduction was due to the enhanced shifting of K+ from the extracellular to the intracellular fluid compartment rather than its removal by dialysis. This finding could have an impact for those patients with life-threatening pre-HD hyperkalaemia.