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Measuring ceruloplasmin
J Lab Clin Med Volume 144, Number 6
Why is this suddenly topical? Endurance athletes have long sought to raise their hemoglobins to a level that would increase the length of time they could function at a high level of exertion. Generally, the optimal performance is seen at a hemoglobin slightly higher than normal; although the incremental gains with increasing the hemoglobin are small, they may be telling at the highest levels of competition. The improved performance comes at a price: a person with an elevated hematocrit may be in real rheological trouble and/or at risk of thrombosis if he becomes dehydrated. “Blood doping” (transfusion for performance enhancement) and the use of erythropoietin are both banned in bicycle racing by the Union Cycliste Internationale; the earliest control measure was simply to ban from competition any rider whose hematocrit exceeded 50%, but more sensitive techniques for detection are being developed and introduced. It has recently been alleged that some world class stage racers have tried to get around this rule by having dedicated (secret) red cell donors, closely matched in major and most minor blood groups to the recipient athlete. Flow cytometric techniques have been applied to the detection of this practice, and a firestorm of controversy has resulted. In theory, flow cytometry could detect a small number of cells with a very minor antigen mismatch—something that would never be found by conventional agglutination techniques. However, the data establishing the specificity of the reagents used have never been published. It’s difficult for an outside observer to know whether the technique is reliable as applied, and it’s difficult for a wrongly accused athlete to mount an effective defense. Our case and the suspect cyclists share the fate of being accused of wrongdoing on the basis of new technologies raising questions about the origin of blood. They provide “food for thought” about the nature of evidence, and the confidence required to act upon evidence once it has been gathered. *Presumably, this name originated with one of the several towns named Münchhausen.
Two technical notes Measuring ceruloplasmin A low level of the plasma copper binding protein, ceruloplasmin, is a diagnostic hallmark of Wilson’s disease. It turns out that there exist inherited abnormalities of ceruloplasmin structure, so some patients with Wilson’s have a normal level of a dysfunctional protein. Ceruloplasmin is an oxidase, and one may also measure its enzymatic activity; this allows detection of the patients who have a structural abnormality rather than a quantitative lack. Comparison of the protein level and the oxidase activity may also allow the prediction of copper deficiency in chelation therapy. (See Macintyre et alii; page 294.)
Breath hydrogen and lactose intolerance Patients who are deficient in lactase tend to deliver more undigested carbohydrate to the lower intestinal tract, where it is metabolized by micro-organisms. The resulting hydrogen may be detected in exhaled air, and may be used to confirm a suspected diagnosis. Eighty-four patients with gastrointestinal diseases underwent breath hydrogen excretion measurement after lactose (to test for lactose malabsorption), after lactulose (to exclude false negative results due to hydrogen nonproducer status), and after a non-absorbable electrolyte solution (to exclude false positive results due to mixing of intestinal content and release of preformed hydrogen entrapped in the feces). A higher proportion of symptomatic patients were found to be abnormal by measuring the hydrogen at multiple time points than was the case when the more conventional approach—a single measurement at six hours—was used. (See Di Stefano et alii; page 313.) For the editors Dale E. Hammerschmidt, MD Editor-in-Chief
279
Why is this suddenly topical? Endurance athletes have long sought to raise their hemoglobins to a level that would increase the length of time they could function at a high level of exertion. Generally, the optimal performance is seen at a hemoglobin slightly higher than normal; although the incremental gains with increasing the hemoglobin are small, they may be telling at the highest levels of competition. The improved performance comes at a price: a person with an elevated hematocrit may be in real rheological trouble and/or at risk of thrombosis if he becomes dehydrated. “Blood doping” (transfusion for performance enhancement) and the use of erythropoietin are both banned in bicycle racing by the Union Cycliste Internationale; the earliest control measure was simply to ban from competition any rider whose hematocrit exceeded 50%, but more sensitive techniques for detection are being developed and introduced. It has recently been alleged that some world class stage racers have tried to get around this rule by having dedicated (secret) red cell donors, closely matched in major and most minor blood groups to the recipient athlete. Flow cytometric techniques have been applied to the detection of this practice, and a firestorm of controversy has resulted. In theory, flow cytometry could detect a small number of cells with a very minor antigen mismatch—something that would never be found by conventional agglutination techniques. However, the data establishing the specificity of the reagents used have never been published. It’s difficult for an outside observer to know whether the technique is reliable as applied, and it’s difficult for a wrongly accused athlete to mount an effective defense. Our case and the suspect cyclists share the fate of being accused of wrongdoing on the basis of new technologies raising questions about the origin of blood. They provide “food for thought” about the nature of evidence, and the confidence required to act upon evidence once it has been gathered. *Presumably, this name originated with one of the several towns named Münchhausen.
Two technical notes Measuring ceruloplasmin A low level of the plasma copper binding protein, ceruloplasmin, is a diagnostic hallmark of Wilson’s disease. It turns out that there exist inherited abnormalities of ceruloplasmin structure, so some patients with Wilson’s have a normal level of a dysfunctional protein. Ceruloplasmin is an oxidase, and one may also measure its enzymatic activity; this allows detection of the patients who have a structural abnormality rather than a quantitative lack. Comparison of the protein level and the oxidase activity may also allow the prediction of copper deficiency in chelation therapy. (See Macintyre et alii; page 294.)
Breath hydrogen and lactose intolerance Patients who are deficient in lactase tend to deliver more undigested carbohydrate to the lower intestinal tract, where it is metabolized by micro-organisms. The resulting hydrogen may be detected in exhaled air, and may be used to confirm a suspected diagnosis. Eighty-four patients with gastrointestinal diseases underwent breath hydrogen excretion measurement after lactose (to test for lactose malabsorption), after lactulose (to exclude false negative results due to hydrogen nonproducer status), and after a non-absorbable electrolyte solution (to exclude false positive results due to mixing of intestinal content and release of preformed hydrogen entrapped in the feces). A higher proportion of symptomatic patients were found to be abnormal by measuring the hydrogen at multiple time points than was the case when the more conventional approach—a single measurement at six hours—was used. (See Di Stefano et alii; page 313.) For the editors Dale E. Hammerschmidt, MD Editor-in-Chief
279