It has long been recognized that certain ordinarily salutary drugs may produce an acute hemolytic anemia in some susceptible individuals. The 8-aminoquinoline antimalarial, pamaquine (plasmoquine), was such a medication. It was the investigation of the hemolytic effect of pamaquine and its derivatives which led to the recognition that hereditary red cell enzyme deficiencies could produce hemolytic disease.

Glucose-6-phosphate dehydrogenase deficiency.

A wide variety of infectious agents has been associated with acute pancreatitis. Strict diagnostic criteria were developed to assess with relationship between individual microorganisms and acute pancreatitis. Pathologic or radiologic evidence of pancreatitis associated with well-documented infection was noted with viruses (mumps, coxsackie, hepatitis B, cytomegalovirus, varicella-zoster virus, herpes simplex virus), bacteria (Mycoplasma, Legionella, Leptospira, Salmonella), fungi (Aspergillus), and parasites (Toxoplasma, Cryptosporidium, Ascaris). Clues to the infectious nature of pancreatitis lay in the characteristic signs and symptoms associated with the particular infectious agent. How often these agents are responsible for idiopathic pancreatitis is unclear.

Infectious Causes of Acute Pancreatitis

The Liver as a Source of Extrarenal Erythropoietin Production

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzyme defect and one of the most common genetic disorders worldwide, with an estimated 400 million people worldwide carrying a mutation in the G6PD gene that causes deficiency of the enzyme. Although drug-induced haemolysis is considered the most common adverse clinical consequence of G6PD deficiency, significant confusion exists regarding which drugs can cause haemolytic anaemia in patients with G6PD deficiency. In the absence of consensus among physicians, patients are subject to conflicting advice, causing uncertainty and distress. In the current review we aimed, by thorough search of the medical literature, to collect evidence on which to base decisions either to prohibit or allow the use of various medications in patients with G6PD deficiency. A literature search was conducted during May 2009 for studies and case reports on medication use and G6PD deficiency using the following sources: MEDLINE (1966-May 2009), PubMed (1950-May 2009), the Cochrane database of systematic reviews (2009), and major pharmacology, internal medicine, haematology and paediatric textbooks. After assessing the literature, we divided medications into one of three groups: medications that should be avoided in individuals with G6PD deficiency, medications that were considered unsafe by at least one source, but according to our review can probably be given safely in normal therapeutic dosages to individuals with G6PD deficiency as evidence does not contravene their use, and medications where no evidence at all was found to contravene their use in G6PD-deficient patients. It is reasonable to conclude that, over time, many compounds have been wrongly cited as causing haemolysis because they were administered to patients experiencing an infection-related haemolytic episode. We found solid evidence to prohibit only seven currently used medications: dapsone, methylthioninium chloride (methylene blue), nitrofurantoin, phenazopyridine, primaquine, rasburicase and tolonium chloride (toluidine blue). Regarding all other medications, our review found no evidence to contravene their use in normal therapeutic doses to G6PD-deficient patients. There is a need for evidence-based global consensus regarding medication use in G6PD-deficient patients.

Medications and glucose-6-phosphate dehydrogenase deficiency: an evidence-based review.

Primary carcinoma of the liver

Polycythemia in Primary Carcinoma of the Liver

Further observations on polycythemia in hepatocellular carcinoma.

A THROMBUS produced in the marginal vein of a rabbit’s ear by the injection of a solution of thrombin, a technique described by Grossi, Cliffton and Cannamela (1954), lyses rapidly. In the course of an investigation of the factors involved in this lysis, Kwaan, Lo and McFadzean (1957a), from observations on human volunteers, concluded that the fibrinolytic activity which developed withm veins resulted from the stimulation of a cholinergic effector mechanism within their walls. Such stimulation reflexly produced fibrinolytic activity withm the rest of the venous tree of the same limb and, commonly, fibrinolytic activity in the veins of the opposite limb. They showed that this effector mechanism was stimulated by adrenaline and ischaemia. In a subsequent communication, Kwaan, Lo and McFadzean (1957b) reported that serotonin (5-hydroxytryptamine) was a stimulus even more potent than either adrenaline or ischaemia. It seemed possible therefore that a clot produced within a vein stimulated, through the serotonin liberated from disintegrating platelets, the cholinergic effector mechanism in the wall of the vein, resulting in the production of fibrinolytic activity w i t h the vein and lysis of the clot. The observations on human volunteers, however, did not afford indication of the intensity of the fibrinolytic activity which might be encountered in vivo. The purpose of this communication is to report experimental observations on rabbits which not only support and extend the above hypothesis but show that the fibrinolytic activity produced is such as to result in the rapid lysis in vivo of whole-blood clots.

A.J.S. McFadzean

Papers

Polycythemia in Primary Carcinoma of the Liver

Further observations on polycythemia in hepatocellular carcinoma.

On the lysis of thrombi experimentally produced within veins.

Observations on the anemia of cryptogenetic splenomegaly. II. Expansion of the plasma volume.

Erythrocytosis associated with hepatocellular carcinoma.