Molecular breakpoint analysis and relevance of variable mosaicism in a woman with short stature,primary amenorrhea,unilateral gonadoblastoma,and a 46,X,del(Y)(q11)/45,X karyotype

Congenital hydrocephalus associated with aqueductal stenosis and/or agenesis of the corpus callosum has been described in newborn males with mutations in L1CAM, a gene that encodes a neural cell adhesion molecule. These males usually have severe mental retardation and may have spastic paraplegia and adducted thumbs. In contrast, Hirschsprung disease, or absence of ganglion cells in the distal gut, has rarely been described in such individuals. We report a male infant who had severe hydrocephalus identified in the prenatal period with evidence of aqueductal stenosis and adducted thumbs at birth. He developed chronic constipation, and rectal biopsy confirmed the diagnosis of Hirschsprung disease. Molecular testing of the L1CAM gene revealed a G2254A mutation, resulting in a V752M amino acid substitution. A common polymorphism in RET, but no mutation, was identified. Our patient represents the third example of coincident hydrocephalus and Hirschsprung disease in an individual with an identified L1CAM mutation. We hypothesize that L1CAM‐mediated cell adhesion may be important for the ability of ganglion cell precursors to populate the gut, and that L1CAM may modify the effects of a Hirschsprung disease–associated gene to cause intestinal aganglionosis. © 2002 Wiley‐Liss, Inc.     

Hyperaemia in rat neocortex produced by acute exposure to methylenedioxymethamphetamine

Cerebral blood flow and glucose utilization were measured in rat neocortex, hippocampus and striatum following methylenedioxymethamphetamine injection (5 mg/kg, i.v.), using the tracers [¹⁴C]iodoantipyrine and [¹⁴C]2-deoxyglucose, respectively. In control rats, blood flow was coupled to glucose metabolism, but in methylenedioxymethamphetamine-treated rats, marked hyperperfusion was measured in frontal and parietal cortex with no change in glucose use. This suggests that methylenedioxymethamphetamine has the potential to disrupt cerebrovascular control.     

Perfluorochemicals as US contrast agents for tumor imaging and hepatosplenography: preliminary clinical results

In animals, perfluorochemicals (PFCs) are effective ultrasound (US) contrast agents that produce hepatic, splenic, and tumor enhancement. The use of Fluosol-DA 20%, an emulsion of perfluorodecalin and perfluorotripropylamine, was studied in nine non-critically ill patients with cancer who had liver lesions. US studies without Fluosol were compared with studies obtained 24, 48, and 72 hours after Fluosol infusion. Vital signs and extensive laboratory analyses are performed before and after Fluosol infusion. Liver metastases from colonic, pancreatic, and gastric carcinoma exhibited rim or diffuse enhancement after a Fluosol dose of 1.6 g/kg or greater. Fluosol produced echogenic enhancement of the liver and spleen relative to kidney at a dose of 2.4 g/kg, allowing the detection of nonenhancing lesions. In addition, Fluosol at a dose of 1.6 g/kg or greater allowed detection of lesions not seen before contrast medium was administered in three of the seven patients studied. There was a mild increase in the level of serum glutamic oxaloacetic transaminase in two patients, one given 2.4 and the other 3.2 g/kg of Fluosol. Mild and transient allergic reactions without change in vital signs were experienced by two patients.     

Rising mortality from motor neurone disease in Sweden 1961–1990: the relative role of increased population life expectancy and environmental factors

Recent studies of mortality from motor neurone disease (MND) in Sweden have demonstrated rising levels of mortality from the disease, especially amongst older age groups. Case-control investigations have suggested that certain environmental factors are significantly related to variations in mortality from the disease, and are associated with a probable individual susceptibility to MND. This study applies an innovative epidemiological technique to longitudinal and cohort analysis of Swedish mortality from MND during the period 1961 to 1990. Survival modelling shows that a subpopulation susceptible to MND exists in Sweden, as has been demonstrated in other countries. The increased life expectancy of the Swedish population since 1961 has resulted in more of that susceptible population living to the ages at which MND is expressed, explaining the majority of the increase in mortality from the disease. However, environmental factors may play a role in accelerating the course of MND and may affect the timing of death within the susceptible sub-population.     

Leukaemic mantle cell lymphoma with t(11;14) and trisomy 12 showing clinical features of state A0 B cell chronic lymphocytic leukaemia

The precise diagnosis of lymphoma usually requires the histological examination of lymph nodes or involved tissues. Mantle cell lymphoma is a form of intermediate grade non-Hodgkin's lymphoma in which typical morphological immunophenotypic and cytogenetic features have been recognised. A case of leukaemic mantle cell lymphoma with the characteristic reciprocal translocation t(11;14) together with trisomy 12, a chromosomal abnormality usually associated with B cell chronic lymphocytic leukaemia (CLL), is presented. This combination of cytogenetic abnormalities has not been reported previously. The lack of lymphadenopathy and hepatosplenomegaly in this patient is more in keeping with stage A0 CLL. This case demonstrates the close clinical and biological relationship between mantle cell lymphoma and CLL.