Carcinoma of the hepaticopancreatic ampullar region: role of US

Hepaticopancreatic ampullar tumors are so called because they are located at the confluence of the bile duct, pancreatic duct, and duodenum. Jaundice is an early sign of the disease and often leads to early diagnosis and favorable prognosis compared with other tumors that occur in this area. Of eight patients who underwent ultrasound (US) in the past 5 years, six (75%) were found to have tumor. The sizes of the tumors ranged from 1.6 to 2 cm. An intraluminal, polypoid mass in the distal part of the common bile duct was seen in four patients. In the other two patients, a sharply delineated mass gave rise to abrupt termination of the distal duct. Improved US resolution, more experience with this modality, and accurate diagnosis of these tumors with US will contribute to improved detection and prompt treatment.     

A comparison of the Outcome Questionnaire‐45 and Outcome Questionnaire‐30 in classification and prediction of treatment outcome

Recent research has found that measuring, monitoring and providing therapists with feedback about their clients' treatment progress improves treatment outcome. This study assessed the level of agreement between two outcome measures used to measure and monitor treatment progress. The Outcome Questionnaire (OQ‐45) was compared with a shorter, derivative measure, the OQ‐30. Each measure has an associated feedback system, which provides therapists with feedback about their clients' treatment progress. The OQ‐45 and the OQ‐30 demonstrated high levels of agreement in measurement of client outcome. The OQ‐45 feedback system emerged as the most accurate and clinically useful method for providing therapists with feedback about their clients' predicted treatment outcomes. Copyright © 2006 John Wiley & Sons, Ltd.     

Circulating melanoma-associated antigens in ocular melanoma

A pilot study was performed to test for melanoma-associated antigens (MAAgs) in the sera of patients with localized uveal melanoma, using monoclonal antibodies (MoAbs). Both whole sera and polyethylene glycol (PEG) 2.5% serum precipitates from 18 patients with clinically localized uveal melanoma and two patients with localized invasive conjuctival melanoma were analyzed for two human cutaneous MAAgs by an enzyme-linked immunosorbent assay (ELISA). These antigens could not be identified when whole sera were used. However, after PEG precipitation, a MoAb specific for the p210 MAAg reacted with four of 20 patient samples and none of 17 controls. A second MoAb specific for the p97a MAAg reacted with one of 20 patients and none of 17 controls. These findings indicate the existence of antigens common to both uveal and cutaneous melanoma and suggest that the refinement of assays to screen sera with a battey of MoAbs may be of value in diagnosing and/or monitoring patients with uveal melanoma. Circulating immune complexes were detected in the sera of six patients but did not correlate with any clinical features or with the presence or absence of detectable MAAgs.     

Progress in the autosomal segmental aneusomy syndromes (SASs): single or multi-locus disorders?

Based on cytogenetic observations, several syndromes have been previously identified as microdeletion-based disorders. In this review, recent progress is presented regarding whether one or multiple genes can be implicated in the pathogenesis of these segmentally aneusomic syndromes. The syndromes discussed include Angelman, Alagille, Williams, Langer-Giedeon, Prader-Willi, Smith-Magenis, Miller-Dieker, and DiGeorge/velocardiofacial or the 22q11 deletion syndromes. For Angelman and Alagille syndromes, single genes have been identified, whereas for Williams and Langer-Giedion syndromes, more than one gene can be implicated. Although there has been significant progress in dissecting the molecular basis for the other disorders, the ultimate answer regarding one versus several genes remains to be determined.      

Missense mutation in a von Willebrand factor type A domain of the alpha 3(VI) collagen gene (COL6A3) in a family with Bethlem myopathy

The Bethlem myopathy is a rare autosomal dominant proximal myopathy characterized by early childhood onset and joint contractures. Evidence for linkage and genetic heterogeneity has been established, with the majority of families linked to 21q22.3 and one large family linked to 2q37, implicating the three type VI collagen subunit genes, COL6A1 (chromosome 21), COL6A2 (chromosome 21) and COL6A3 (chromosome 2) as candidate genes. Mutations of the invariant glycine residues in the triple-helical domain-coding region of COL6A1 and COL6A2 have been reported previously in the chromosome 21-linked families. We report here the identification of a G-->A mutation in the N-terminal globular domain-coding region of COL6A3 in a large American pedigree (19 affected, 12 unaffected), leading to the substitution of glycine by glutamic acid in the N2 motif, which is homologous to the type A domains of the von Willebrand factor. This mutation segregated to all affected family members, to no unaffected family members, and was not identified in 338 unrelated Caucasian control chromosomes. Thus mutations in either the triple-helical domain or the globular domain of type VI collagen appear to cause Bethlem myopathy.      

doublecortin is the major gene causing X-linked subcortical laminar heterotopia (SCLH)

Subcortical laminar heterotopia (SCLH), or 'double cortex', is a cortical dysgenesis disorder associated with a defect in neuronal migration. Clinical manifestations are epilepsy and mental retardation. This disorder, which mainly affects females, can be inherited in a single pedigree with lissencephaly, a more severe disease which affects the male individuals. This clinical entity has been described as X- SCLH/LIS syndrome. Recently we have demonstrated that the doublecortin gene, which is localized on the X chromosome, is implicated in this disorder. We have now performed a systematic mutation analysis of doublecortin in 11 unrelated females with SCLH (one familial and 10 sporadic cases) and have identified mutations in 10/11 cases. The sequence differences include nonsense, splice site and missense mutations and these were found throughout the gene. These results provide strong evidence that loss of function of doublecortin is the major cause of SCLH. The absence of phenotype-genotype correlations suggests that X-inactivation patterns of neuronal precursor cells are likely to contribute to the variable clinical severity of this disorder in females.