Bleeding problems in patients with liver disease. Ways to manage the many hepatic effects on coagulation.

Liver disease is associated with a wide variety of abnormalities of the coagulation system and often with severe bleeding. Knowledge of the effects of liver disease and its complications on the various clotting factors may be useful in differential diagnosis. Therapy is difficult but should be approached in a stepwise fashion, with attention to the potential hazards of each intervention. The coagulation system and its interrelationship with liver function can be complex. To ensure the best care of patients with liver disease and bleeding, primary care physicians should not hesitate to enlist the assistance of specialists in clotting disorders and a reliable coagulation laboratory.

The role of 2-chlorodeoxyadenosine in the treatment of patients with refractory angioimmunoblastic lymphadenopathy with dysproteinemia.

Treatment of patients with angioimmunoblastic lymphadenopathy with dysproteinaemia (AILD) often constitutes a challenge for the clinical haematologist. Single-agent and combination chemotherapy have failed to increase the response rate or survival of patients with AILD. A total of seven patients with refractory or relapsed AILD were treated with 2-chlorodeoxyadenosine (2-CdA) for variable number of cycles. The overall response rate was 57% with two patients (28.5%) achieving complete and sustained response. 2-Chlorodeoxyadenosine appears to be an active agent for patients with previously treated AILD. Phase II studies evaluating the efficacy of this agent as front-line treatment for AILD are justified, especially in the absence of any effective therapy for this disorder.

The observation-holding area; a prospective study.

Although emergency department observation-holding units have been shown to be effective in limiting hospitalizations and improving the accuracy of disposition, the possibility of adverse outcome following discharge from such units has not been addressed. To establish the safety of the unit, a five-month prospective study of all patients admitted to this area was carried out and included long-term follow-up. There were 442 patients admitted. Of these, 78% were discharged improved. Complications in the unit were minimal and there were no deaths. Long-term follow-up revealed four deaths (1%) and four patients (1%) who had complicated hospitalizations. Diagnosis, age, patient condition, and time of admission to the unit were predictive of the need for inpatient hospitalization. We conclude that the observation-holding unit, with appropriate supervision, represents a safe alternative disposition for selected emergency patients.

Suicidal overdoses with hypoglycemic agents.

Suicide attempts using hypoglycemic agents are uncommon but are associated with a high level of morbidity and mortality. Their recognition is sometimes difficult and the duration of hypoglycemic effect is often prolonged. Two cases that illustrate the difficulties encountered in recognition and therapy are described. Effective therapy depends on adequate glucose supplementation to maintain euglycemia. Therapeutic intervention often must be maintained for several days. Glucocorticoids may be useful in difficult cases. Other modes of therapy, including glucagon, are unproven or controversial.

The mechanism of folate transport in rabbit reticulocytes.

Folate transport in phenylhydrazine-induced rabbit reticulocytes was studied with the non-metabolized folate-analog, methotrexate. The time-course of methotrexate uptake into a mixed population of reticulocytes and mature erythrocytes is a two-component process consisting of a small, but rapid, initial uptake phase followed by a much slower uptake component which remains essentially constant over the period of observation. The velocity of the latter uptake component is directly proportional to the per cent reticulocytes and appears to represent a unidirectional influx of methotrexate into these cells. Uptake of methotrexate into reticulocytes was found to have the following characteristics: (a) temperature sensitivity, Q(10) of 4; (b) uptake velocity as a function of the extracellular methotrexate concentration approximated Michaelis-Menten kinetics with a maximum transport velocity of 48 pmoles/min per g dry wt; the extracellular methotrexate level at which the uptake velocity was one-half maximum was 1.4 muM; (c) 5-formyltetrahydrofolate markedly inhibited methotrexate uptake but pteroylglutamic acid inhibition was weak; (d) uptake was stimulated in cells preincubated with 5-formyltetrahydrofolate, indicative of hetero-exchange diffusion; (e) uptake was independent of extracellular sodium but was inhibited by anions including nitrate, phosphate, and glucose-6-phosphate; (f) uptake was enhanced by azide plus iodoacetate. These data indicate that folate transport in rabbit reticulocytes is mediated by a carrier mechanism which disappears with reticulocyte maturation. The mechanism of folate transport in rabbit reticulocytes is qualitatively similar to tumor cells previously studied; both appear to have an energy-dependent mechanism limiting folate uptake, and influx in both is inhibited by structurally unrelated inorganic and organic anions. These studies suggest that circulating pteroylglutamic acid is of little importance in meeting the folate requirements of folate-dependent tissues and raise the possibility that clinical conditions associated with alterations in the anionic composition of the blood may be accompanied by impaired utilization of the folates.