Life-threatening hyperkalemia associated with captopril administration.

Angiotensin converting enzyme (ACE) inhibitors have become commonly used medications for hypertension and congestive heart failure. These agents are noted for their low incidence of adverse effects; but in certain cases, these effects can be life-threatening. Severe hyperkalemia is one of the potentially dangerous effects of the ACE inhibitors. While cases of life-threatening hyperkalemia associated with the use of ACE inhibitors have been described previously, in no instance was dialysis required. Herein, we report a case of acute hyperkalemia in a patient with congestive heart failure and renal insufficiency, the resolution of which required hemodialysis. The hyperkalemia in this case occurred without an increase in the patient's azotemia. In addition, the patient did not respond to attempts to effect the intracellular shift of potassium. This suggested that there may have been a defect in internal potassium homeostasis.

Defective release of vascular plasminogen activator in patients with gynecologic malignancies.

Vascular plasminogen activator release was measured in 176 women with gynecologic malignancies and 92 normal women. Releasable plasminogen activator was considerably decreased in the patients (P less than 0.00001 by Wilcoxon's rank sum test) with 59.1% releasing less than 0.04 Committee on Thrombolytic Agents units per milliliter of plasma after a standard venous occlusion procedure. The data were also stratified by tumor location, demonstrating that this decrease in releasable vascular plasminogen activator was seen for ovarian (P = 0.0001), endometrial (P = 0.0017), and cervical (P = 0.0063) cancers. Postoperative deep vein thrombosis, with or without pulmonary emboli, occurred in 28 patients (15.9% incidence). These patients also demonstrated markedly lower levels of releasable vascular plasminogen activator compared to control subjects (P less than 0.0001). It is suggested that defective release of vascular plasminogen activator contributes to a hypercoagulable state in patients with gynecologic malignancies and predisposes to postoperative thromboembolic complications.

Release of tissue plasminogen activator and its fast-acting inhibitor in defective fibrinolysis.

Releasable tissue plasminogen activator (t-PA) and the fast inhibitor of t-PA were measured in 18 controls and a pedigree with venous thrombosis. The functional assay was performed by a technique that destroys the t-PA inhibitor when blood is drawn. It was found that activator and inhibitor levels varied widely in the control group. One patient demonstrated inhibitor levels, on two different occasions, of 2.82 and 3.54 IU of t-PA per milliliter of plasma, as compared with a releasable activator level of 1.87 IU/mL. The t-PA antigen levels of this patient and the remainder of the pedigree were essentially normal for all seven subjects. Thus, it is suggested that the previously reported fibrinolytic disorder in this pedigree represents an imbalance between activator and inhibitor levels rather than an actual deficiency of t-PA.

Releasable vascular plasminogen activator and thrombotic strokes.

Releasable vascular plasminogen activator was measured in 28 patients (14 males and 14 females) with a history of thrombotic strokes documented by computed tomographic scanning. Levels were compared with those in a control population of 126 healthy subjects with no history of thromboembolic disease. The patient population tended to have higher levels of activator than the control population, 0.53 Committee on Thrombolytic Agents (CTA) units/ml of plasma for patients versus 0.21 CTA units/ml for control subjects; however, there was a wide distribution of values, as reported in all previous populations. Since plasminogen activator levels distribute in a non-Gaussian manner, patient values and control values were stratified into deciles. By this approach, the distribution among the patient was not significantly different from that among the control subjects except in females, who demonstrated skewing to higher deciles (p = 0.019). It is concluded that thrombotic strokes are not associated with low levels of releasable vascular plasminogen activator, and in fact, these patients may present with levels considerably above the mean for normal subjects.

L-[3H]Glutamate binding to hippocampal synaptic membranes: two binding sites discriminated by their differing affinities for quisqualate.

The excitatory glutamate analogs quisqualate and ibotenate were employed to distinguish multiple binding sites for L-[3H]glutamate on freshly prepared hippocampal synaptic membranes. The fraction of bound radioligand that was displaceable by 5 microM quisqualate was termed GLU A binding. That which persisted in the presence of 5 microM quisqualate, but was displaceable by 100 microM ibotenate, was termed GLU B binding. GLU A binding equilibrated within 5 min and remained unchanged for up to 80 min. GLU B binding appeared to equilibrate at least as rapidly, but incubation with ligand unmasked latent binding sites. Saturation binding curves were best fitted by single exponentials, which yielded KD values of about 200 nM (GLU A) and 1 microM (GLU B). On the average, GLU B binding sites were about twice as abundant in these membranes as were GLU A sites. Rapid freezing of the membranes, followed by storage at -26 degrees C and rapid thawing markedly diminished GLU A binding, but nearly tripled GLU B binding. Both site bound L-glutamate with 10-30 times the affinity of D-glutamate. The GLU A site also bound L-glutamate with about 10 times the affinity of L-aspartate and discriminated poorly between L- and D-aspartate. In contrast, the GLU B site bound L-aspartate with an affinity similar to that for L-glutamate, and with an order-of-magnitude greater affinity than D-aspartate. The structural specificities of the GLU A and GLU B binding sites suggest that these sites may correspond to receptors on hippocampal pyramidal cell dendrites that are activated by iontophoretically applied L-glutamate.