Need For Additional Diagnostic Testing Research Articles

Understanding the Superior Clear Space in the Adult Ankle

The width of the medial clear space often is used to determine the integrity of the deltoid ligament, the primary medial stabilizer of the ankle joint. The normal clinical relationship of the superior clear space to the medial clear space is not well described. This investigation sought to determine if the superior clear space constitutes an accurate point of comparison for the medial clear space and a means for assessing ligamentous stability in an adult ankle. A retrospective review of consecutive ankle radiographs for a 4-month period of time was completed using a university-based radiology database. Using a digitally calibrated ruler, the widths of the medial and superior clear spaces were measured on the mortise view. These values were compared using a Student's t-test. Digital radiographs of 564 consecutive ankles were reviewed retrospectively and 94 cases were without evidence of trauma, surgery, or degenerative disease. The medial and superior clear spaces were measured on the mortise view and found to be 2.7 mm (standard deviation 0.5; range 1.3 mm to 4.3 mm; 95% confidence interval 1.7 mm to 3.8 mm) and 3.6 mm (standard deviation 0.6; 2.0 to 5.3; CI 2.4 mm to 4.7 mm), respectively. The average absolute difference was 0.9 mm (standard deviation 0.5; -0.7 to 1.5; CI -0.1 mm to 1.8 mm) and in 92 of 94 ankles (98%), the superior clear space was greater than or equal to the medial clear space. Understanding the normal radiographic relationship of the superior and medial clear spaces may help in the diagnosis of ligamentous instability in the ankle and may obviate the need for additional diagnostic tests.

Genotype-phenotype study in an FSHD family with a proximal deletion encompassing p13E-11 and D4Z4

In the majority of facioscapulohumeral muscular dystrophy (FSHD) cases, the molecular basis of the disease is due to loss of subtelomeric D4Z4 repeat units at 4q35. Occasionally, an apparent absence of the contracted D4Z4 repeat is associated with FSHD. One explanation for this finding is a deletion in the region proximal to the D4Z4 repeat array that encompasses the p13E-11 (D4F104S1) probe-binding site used in the DNA diagnosis. The frequency of such proximally extended deletions is unknown, and to date, few patients have been described due to the difficulties in the molecular identification of such cases. We describe a family (DUK 2531) in which a contracted D4Z4 allele and a large proximal deletion of approximately 75 kb are segregating to 11 individuals. This is the largest deletion identified to date. Family DUK 2531 was initially thought to have normal D4Z4 fragment size and therefore unlinked to the 4q35 region (FSHD1B). Further molecular analysis of DUK 2531 reveals the presence of 10 repeat units (33 kb). The extended deletion includes the probe p13E-11 and B31 binding sites, the inverted repeat D4S2463, and genes FRG2 and TUBB4Q. Despite the length of the proximal deletion in this family, the range and severity of the clinical manifestations are typical for the disorder. Because such deletions can lead to misinterpretation in the diagnostic setting, this suggests the need for additional diagnostic tests in facioscapulohumeral muscular dystrophy.

Diagnosis of cobalamin deficiency I: Usefulness of serum methylmalonic acid and total homocysteine concentrations

The serum cobalamin assay is the primary diagnostic test for cobalamin deficiency. It appears to be an excellent screening test since most patients with clinically confirmed cobalamin deficiency have low levels. Recent studies indicate that the clinical picture of cobalamin deficiency is much more diverse than previously believed. It is also apparent that many patients with low serum cobalamin concentrations are not cobalamin deficient. Thus, there is a need for additional diagnostic tests to further distinguish patients with low serum cobalamin levels who are actually cobalamin deficient and will benefit from lifetime treatment from those who are not deficient and will not benefit. Serum levels of methylmalonic acid and total homocysteine have been shown to be markedly elevated in most patients with cobalamin deficiency, and total homocysteine concentrations are markedly elevated in most patients with folate deficiency. The levels of these metabolites fall to normal if these patients are treated with the appropriate vitamin but remain essentially unchanged if the wrong vitamin is administered. These observations demonstrate that serum methylmalonic acid and total homocysteine levels are useful in diagnosing patients with cobalamin and folate deficiency and in distinguishing between these two vitamin deficiencies.