Screening for hemochromatosis: high prevalence and low morbidity in an unselected population of 65,238 persons.

BACKGROUND: Hereditary hemochromatosis (HH) is a common genetic disease leading to accumulation of iron in several organs, most notably the liver. The C282Y/C282Y mutation in the HFE gene is found in most cases. In order to prevent clinical disease and to study the cost and feasibility of screening, a large population was screened. METHODS: In a Norwegian county, all inhabitants 20 years or older were invited to participate in a population-based health survey programme. Screening for HH was one of several subprojects. Blood samples were obtained from 65,238 persons. Subjects with high serum transferrin saturation in two tests and high serum ferritin were clinically evaluated for HH. All subjects with high serum transferrin saturation in two tests were offered genotyping. RESULTS: HH was newly diagnosed in 92 women and 177 men. Phlebotomy treatment was performed in 64 women and 152 men. Severe organ damage (liver cirrhosis) was ascertained in only 4 men. We found no correlation between serum ferritin and age. The estimated cost was US$ 1.6 per subject screened and US$ 390 per newly discovered HH subject. The estimated prevalence of phenotypical HH not previously known was 0.34% in women and 0.68% in men. The prevalence of the C282Y/C282Y mutation was at least 0.68%. CONCLUSION: Large-scale screening for HH can be performed at a relatively low cost if combined with a health survey programme. The yield in terms of newly discovered cases is considerable, but few cases were found seriously ill. Better knowledge of the natural course of HH is necessary if we are to be able to estimate the cost-effectiveness of large-scale screening.

Axillary lymph node metastases in breast cancer: preoperative detection with dynamic contrast-enhanced MRI.

Metastatic involvement of axillary lymph nodes is one of the most important prognostic variables in breast cancer. The aim of our work was to study the value of dynamic contrast-enhanced MR imaging in revealing axillary lymph node metastases from breast cancer. A total of 65 patients with invasive breast cancer treated with axillary lymph node dissection were preoperatively evaluated by MRI. T1-weighted dynamic contrast-enhanced 3D images were acquired using a coil covering the breast and the axilla. The dynamic contrast enhancement, size, and morphology of the axillary lymph nodes were registered. Histopathological examination revealed axillary lymph node metastases in 24 patients. When using a signal intensity increase in the lymph nodes of >100% during the first postcontrast image as a threshold for malignancy, 57 of 65 patients were correctly classified (sensitivity 83%, specificity 90%, accuracy 88%). These results were not improved when lymph node size and morphology were used as additional criteria. Axillary lymph nodes can be evaluated as a part of an MR-mammography study without substantial increase in examination time, and provide the surgeon with knowledge about the localization of possible metastatic lymph nodes.

Breast lesions: evaluation with dynamic contrast-enhanced T1-weighted MR imaging and with T2*-weighted first-pass perfusion MR imaging.

PURPOSE: To evaluate the diagnostic value of an imaging protocol that combines dynamic contrast-enhanced T1-weighted magnetic resonance (MR) imaging and T2*-weighted first-pass perfusion imaging in patients with breast tumors and to determine if T2*-weighted imaging can provide additional diagnostic information to that obtained with T1-weighted imaging. MATERIALS AND METHODS: One hundred thirty patients with breast tumors underwent MR imaging with dynamic contrast-enhanced T1-weighted imaging of the entire breast, which was followed immediately with single-section, T2*-weighted imaging of the tumor. RESULTS: With T2*-weighted perfusion imaging, 57 of 72 carcinomas but only four of 58 benign lesions had a signal intensity loss of 20% or more during the first pass, for a sensitivity of 79% and a specificity of 93%. With dynamic contrast-enhanced T1-weighted imaging, 64 carcinomas and 19 benign lesions showed a signal intensity increase of 90% or more in the first image obtained after the administration of contrast material, for a sensitivity of 89% and a specificity of 67%. CONCLUSION: T2*-weighted first-pass perfusion imaging can help differentiate between benign and malignant breast lesions with a high level of specificity. The combination of T1-weighted and T2*-weighted imaging is feasible in a single patient examination and may improve breast MR imaging.

Familial mydriasis, cardiac arrhythmia, respiratory failure, muscular weakness and hypohidrosis.

OBJECTIVES: To describe a family with some sort of progressive autonomic failure in one generation (2 affected of a sibship of 7 sisters). The main features were: mydriasis, cardiac arrhythmia, cardiomegaly, hypohidrosis, respiratory failure, and muscular weakness. METHODS: Pupillometry, evaporimetry, and isokinetic power measurements were carried out. RESULTS: The autonomic dysfunction pattern (mainly cardiac abnormalities, mydriasis) seems to differ somewhat from that of progressive autonomic failure (Shy-Drager syndrome). "Lewy body-like" inclusions were present, in particular in substantia nigra, but also in locus ceruleus and raphe nuclei (cell loss only in locus ceruleus). There were no oligodendroglial, cytoplasmatic inclusions, apparently a marker in multiple system atrophy. Proper Lewy bodies were also present. Differences seemed to prevail vs the Shy-Drager syndrome. Various traits: muscular weakness pattern (e.g. preferential peroneal distribution), minor elbow contractures, and arrhythmia were reminiscent of Emery-Dreifuss muscle dystrophy (E-D). Distinguishing features included: hereditary pattern, mydriasis, and hypohidrosis. CONCLUSION: Conceivably, this disorder is close to, but still not identical with E-D.

Differentiating benign and malignant breast lesions with T2*-weighted first pass perfusion imaging.

PURPOSE: Invasive breast carcinomas and fibroadenomas are often difficult to differentiate in dynamic contrast-enhanced T1-weighted MR imaging of the breast, because both tumors can enhance strongly after contrast injection. The purpose of this study was to evaluate whether the addition of T2*-weighted first pass perfusion imaging can increase the differentiation of malignant from benign lesions. MATERIAL AND METHODS: Nine patients with invasive carcinomas and 10 patients with contrast enhancing fibroadenomas were examined by a dynamic contrast-enhanced T1-weighted 3D sequence immediately followed by a single slice T2*-weighted first pass perfusion sequence positioned in the contrast-enhancing lesion. RESULTS: The carcinomas and the fibroadenomas were impossible to differentiate based on the contrast enhancement characteristics in the T1-weighted sequence. The signal loss in the T2*-weighted perfusion sequence was significantly stronger in the carcinomas than in the fibroadenomas (p = 0.0004). CONCLUSION: Addition of a T2*-weighted first pass perfusion sequence with a high temporal resolution can probably increase the differentiation of fibroadenomas from invasive carcinomas in contrast-enhanced MR imaging of the breast.