Somatic deletion of the imprinted 11p15 region in sporadic persistent hyperinsulinemic hypoglycemia of infancy is specific of focal adenomatous hyperplasia and endorses partial pancreatectomy

Sporadic persistent hyperinsulinemic hypoglycemia of infancy (PHHI) or nesidioblastosis is a heterogeneous disorder characterized by profound hypoglycemia due to inappropriate hypersecretion of insulin. An important diagnostic goal is to distinguish patients with a focal hyperplasia of islet cells of the pancreas (FoPHHI) from those with a diffuse abnormality of islets (DiPHHI) because management strategies differ significantly. 16 infants with sporadic PHHI resistant to diazoxide and who underwent pancreatectomy were investigated. Selective pancreatic venous sampling coupled with peroperative surgical examination and analysis of extemporaneous frozen sections allowed us to identify 10 cases with FoPHHI and 6 cases with DiPHHI. We show here that in cases of FoPHHI, but not those of DiPHHI, there was specific loss of maternal alleles of the imprinted chromosome region 11p15 in cells of the hyperplastic area of the pancreas but not in normal pancreatic cells. This somatic event is consistent with a proliferative monoclonal lesion. It involves disruption of the balance between monoallelic expression of several maternally and paternally expressed genes. Thus, we provide the first molecular explanation of the heterogeneity of sporadic forms of PHHI such that it is possible to perform only partial pancreatectomy, limited to the focal somatic lesion, so as to avoid iatrogenic diabetes in patients with focal adenomatous hyperplasia.     

Squamous cell carcinoma of the prostate: case report and review of literature

Carcinoma of the prostate, that is adenocarcinoma, is one of the most common malignancies in the male with an estimated incidence for 1991 of 122,000 new cases. On the other hand, squamous cell carcinoma of the prostate, with a median incidence of .5%-1% of all prostatic malignancies, has a similar clinical presentation but differs in treatment response and prognosis. We herein present one case of this histological pattern and review the literature pertaining to it.     

The usefulness of the timeliness of endoscopic sphincterotomy in severe acute pancreatitis of biliary origin

There are evidence indicating that endoscopic retrograde cholangiopancreatography with sphincterotomy (ERCP+S) reduces the rate of complications in patients with severe acute biliary pancreatitis (ABP). The aim of this study was to analyze our experience in the treatment of severe ABP with ERCP+S and compare the evolution of the patients treated early (3 days or less following admission) with those treated late (after the 3rd day). A retrospective review of the clinical histories of the 16 patients with severe ABP treated with ERCP+S over the last two years is presented, analyzing their clinical features on admission and evolution. Biliary stones or biliary sludge was observed in 11 cases (69%). Nine patients had undergone early, and 7 late, ERCP+S. The patients of the latter group presented a greater number of complications during evolution than the former group (43% vs 0%; p = 0.025). The mortality of the patients of the late ERCP+S was also greater although without statistical significance (28.6% vs 0%; p = 0.15). No complication secondary to ERCP+S was detected. These findings confirm the fact that ERCP+S performed early in severe ABP significantly reduces the number of complications and is associated with a lower mortality.     

Alpha-tocopherol as a modulator of smooth muscle cell proliferation

The effects of alpha-tocopherol and beta-tocopherol have been studied in rat and human aortic smooth muscle cells. Alpha-tocopherol, but not beta-tocopherol, inhibited smooth muscle cell proliferation and protein kinase C in a dose-dependent manner, at concentrations ranging from 10 to 50 microM. Beta-tocopherol added simultaneously with alpha-tocopherol prevented both proliferation and protein kinase C inhibition. Protein kinase C inhibition was cell cycle-dependent and it was prevented by okadaic acid, a protein phosphatase inhibitor. Protein kinase C activity measured from aortas of cholesterol-fed rabbits was also inhibited by alpha-tocopherol. By using protein kinase C (PKC) isoform-specific inhibitors and immunoprecipitation reactions it was found that PKC-alpha was selectively inhibited by alpha-tocopherol. Further, an activation of protein phosphatase 2A by alpha-tocopherol was found, which caused PKC-alpha dephosphorylation and inhibition. Ultimately, this cascade of events at the level of cell signal transduction leads to the inhibition of smooth muscle cell proliferation.     

Cloning and disruption of the antigenic catalase gene of Aspergillus fumigatus

Aspergillus fumigatus possesses two catalases (described as fast and slow on the basis of their electrophoretic mobility). The slow catalase has been recognized as a diagnostic antigen for aspergillosis in immunocompetent patients. The antigenic catalase has been purified. The enzyme is a tetrameric protein composed of 90-kDa subunits. The corresponding cat1 gene was cloned, and sequencing data show that the cat1 gene codes for a 728-amino-acid polypeptide. A recombinant protein expressed in Pichia pastoris is enzymatically active and has biochemical and antigenic properties that are similar to those of the wild-type catalase. Molecular experiments reveal that CAT1 contains a signal peptide and a propeptide of 15 and 12 amino acid residues, respectively. cat1-disrupted mutants that were unable to produce the slow catalase were as sensitive to H2O2 and polymorphonuclear cells as the wild-type strain. In addition, there was no difference in pathogenicity between the cat1 mutant and its parental cat1+ strain in a murine model of aspergillosis.     

Visual impairment in Swedish children. III. Diagnoses

PURPOSE: To gain an overview of the spectrum of diagnoses among Swedish visually impaired children. METHODS: An epidemiological study of all known visually impaired children was made by review of medical records. RESULTS AND CONCLUSION: In all we found 2373 children, 0-19 years of age, with an age-specific prevalence of 10.9/10,000. The two largest diagnostic groups included neuro-ophthalmological and retinal diseases. The most frequent disorders were cerebral visual impairment, non-hereditary optic atrophy, retinal dystrophy (when regarded as a general entity), congenital hypoplasia of the optic nerve and congenital cataract. Nystagmus secondary to brain disorder, albinism, congenital nystagmus, retinopathy of prematurity and high myopia were also found in a considerable number of patients. The leading diagnoses in children with WHO-defined childhood blindness were non-hereditary optic atrophy, cerebral visual impairment and retinopathy of prematurity. A large proportion of the children, especially in the groups with neuro-ophthalmological disorders and malformations of the posterior segment had additional impairments, emphasizing the importance of a multi-disciplinary approach when assessing multi-handicapped children.     

Human recombinant anti-Rh(D) monoclonal antibodies: improvement of biological properties by in vitro class-switch

The aim of this study was to investigate how intrauterine growth retardation affects body proportions in VLBW infants. The cohort consisted of 135 surviving and 80 deceased preterm infants weighing less than 1250 grams at birth. Gestational age varied between 24 and 36 weeks (mean age 29.7 and 27.5 weeks, respectively). Birth weight was more than 2 SD below the mean birth standard values in 32% of the surviving, and in 27% of the deceased infants. Reduction of weight, length and head circumference at birth was analysed using Z scores based on Swedish birth standards. Z scores of weight, length and head circumference were highly correlated in the surviving and the deceased infants (r = 0.78 to 0.94 and 0.65 to 0.97, respectively). Length was significantly more affected by growth retardation than weight. Weight and head circumference were proportionately reduced. Intrauterine growth retardation influences body proportions in VLBW infants differently than in larger preterm and term infants.     

In times of survival, the right of silence

The purpose of this study was to assess cortical and cancellous bone responses to unilateral limb immobilization and, subsequently, to remobilization with exercise, in a young adult canine model. Right forelimbs of 14 1-2-year old mongrel dogs were immobilized in a non-weight-bearing position by a bandage for 16 weeks. Six control dogs were untreated. At 16 weeks, seven immobilized and three control dogs were euthanized. The remaining seven immobilized dogs began a recovery protocol consisting of 16 weeks of kennel confinement (without the right forelimb bandaged) followed by 16 weeks of treadmill exercise conducted three times per week. These seven dogs and three control dogs were euthanized at 48 weeks. Bone mineral density of the proximal radii was determined with dual-energy X-ray absorptiometry and humeral middiaphyseal cross-sectional areas were determined with computed tomography. Humeri were tested in cranio-caudal three-point bending to failure. Cancellous bone cores from the lateral humeral condyles had wet apparent density determined and were tested to failure in compression. Mechanical properties, bone density, and cross-sectional areas were compared between immobilized (right forelimb), contralateral weight bearing (left forelimb), and control forelimbs with Kruskal-Wallis and post hoc tests. At 16 weeks, bone mineral density, cortical load, yield, and stiffness as well as cancellous bone failure stress, yield stress, and modulus were significantly lower (p < 0.02) for immobilized limbs than control limbs. Immobilized limb cancellous bone mechanical properties were 28%-74% of control values, and cortical bone mechanical properties were 71%-98% of control values. After 32 weeks of remobilization, cortical and cancellous bone mechanical properties were not different from control values except that cortical bone failure stress and modulus were significantly higher (p < 0.01) between remobilized and control limbs. In summary, 16 weeks of forelimb immobilization was associated with significantly lower mechanical properties, and with greater differences in cancellous than cortical bone properties. Mechanical properties were not different from control values after 32 weeks of recovery that included 16 weeks of treadmill exercise.