Acquired non hypertrophic pyloric stenosis in children]

Pediatric non hypertrophic pyloric stenosis (NHPS) are uncommon. Their causes and treatments are debated.Material and methodRetrospective review of all cases of NHPS from 3 pediatric surgery services during the period 1984–2002.ResultsSix children, aged 17 months to 15 years, underwent surgery for NHPS. Clinical symptoms, food vomiting and loss of weight, were present for several weeks before the diagnosis of NHPS was made. The diagnosis was peptic stenosis in 3 cases and has not been established in 3 cases. Search for Helicobacter pylori was negative in all cases. Failure of specific medical treatment and endoscopic dilatations led to pyloric resection in 3 cases and pyloroplasty in 3 cases. Post operative course was uneventful with normal oral feeding and normalisation of weight status. Histologic data were aspecific. No recurrence was observed.DiscussionWe discuss the origin of the pyloric stenosis, regarding clinical, operative and pathological data: were the stenosis the cause or consequence of peptic ulcer? Peptic disease is always advocated, but difficult to prove and may be excessively incriminated. Late symptomatic congenital and acquired idiopathic pyloric stenosis should be recalled. In all cases of proved pyloric stenosis, after failure of medical and endoscopic treatment, a simple surgical procedure (pyloroplasty) associated with medical treatment seems to be effective.ConclusionThe diagnosis of NHPS should be suspected in a child with food vomiting and loss of weight if his age is not concordant with hypertrophic pyloric stenosis. Upper gastro-intestinal series and endoscopy are diagnostic. The precise cause of the stenosis is more difficult to asses. When the medical treatment fails, a pyloroplasty is usually curative.     

Application of magnetic resonance imaging to evaluation of femoral neck structure in growing girls.

Conventional density measures by dual-energy X-ray absorptiometry (DXA) are confounded by increases in bone size and do not assess bone geometry. We assessed precision of magnetic resonance imaging (MRI) and used MRI, DXA, and hip structure analysis (HSA) to assess 7-mo changes in bone structure at the femoral neck in 18 prepubertal girls. At baseline, girls were 10.4 (0.5) yr, 144.0 (8.2) cm, and 35.2 (7.0) kg, on average. Total bone and cortical cross-sectional area (ToA and CoA) were calculated from high-resolution T1-weighted MRI oblique axial images of the femoral neck. We used proximal femur DXA scans (Hologic QDR-4500) and the HSA program to estimate bone cross-sectional area (CSA), and calculate section modulus. MRI precision was determined by scanning 10 volunteers (13-46 yr old) three times with and without repositioning. Precision (CVrms) was 2% for ToA and 7% for CoA. Significant correlations were observed between FN area and MRI-derived ToA (r = 0.57, p = 0.013) and CoA (r = 0.47, p = 0.050). There were significant positive changes over 7 mo by both methods. In conclusion, MRI provides useful information on femoral neck bone area in children. The reproducibility of cortical dimensions at the femoral neck needs improvement through technical modifications and appropriate analysis software.     

A complementarity-determining region peptide of an anti-desmosome autoantibody may interact with the desmosomal plaque through molecular mimicry with a cytoplasmic desmoglein 1 sequence

The sera of patients with pemphigus, a group of autoimmune blistering skin diseases, contain autoantibodies directed against components of adhering junctions termed desmosomes. F12, a human monoclonal antibody derived from a pemphigus patient, recognizes an unknown polypeptide of the desmosomal and hemidesmosomal plaques. The third complementarity-determining region of the F12 heavy chain (VH-CDR3) was shown to share a four-amino-acid sequence (GSSG) with the intracellular domains of desmoglein 1 and bullous pemphigoid antigen 2 which interact with components of, respectively, the desmosomal and hemidesmosomal plaques. Computer modeling of F12 showed that the GSSG sequence protudes inside the antigen-combining site and thus might be involved in antigen interactions. The GSSG sequence is essential to F12 function, since a peptide containing the VH-CDR3 inhibited its binding to target antigens while VH-CDR3 peptides with specific modifications of the GSSG sequence did not. These data allow us to hypothesize that certain autoantibodies produced during the course of an autoimmune disease can behave as adhesion molecules, through the molecular mimicry of the motif involved in protein/protein adhesion, and to propose a new self-antigen binding mechanism for some autoantibodies.     

Differential apoptotic response of J774 macrophages to alumina and ultra-high-molecular-weight polyethylene particles.

We recently identified apoptosis in in vitro wear particle-stimulated macrophages. The recent explosion of interest in apoptosis lies in the fact that it is under positive and negative regulation through evolutionary conserved biochemical pathways. It may also be possible to modulate macrophage apoptosis in the treatment of periprosthetic osteolysis. The purpose of this study was to compare the macrophage response to identically sized particles of alumina ceramic (Al2O3) and ultra-high-molecular-weight polyethylene (UHMWPE) in terms of TNF-alpha release and induction of apoptosis. J774 mouse macrophages were incubated for 0-24 h in the presence of Al2O3 and UHMWPE particles. TNF-alpha release was measured by ELISA; Poly(ADP-ribose)polymerase (PARP) and caspase-3 expression was analyzed by Western blot; DNA fragmentation (DNA laddering) was visualized on agarose gel containing ethidium bromide. Al2O3 particles induced TNF-alpha release after 4 h incubation with concentrations reaching 483 and 800 pg/ml after 24 h with 125 and 250 particles/macrophage, respectively (control = 161 pg/ml) (P < 0.05 vs. control). The same concentrations of UHMWPE particles induced a much larger and significant TNF-alpha release after only 1 h incubation, increasing up to 6250 pg/ml after 24 h (P < 0.05 vs. control). Western blot analysis demonstrated that the active caspase-3 fragment (17 kDa) and the proteolytic PARP fragment (85 kDa) were expressed after 2 h incubation with 125 and 250 Al2O3 particles/macrophage. The active caspase-3 and the PARP fragment had lower expression and appeared after a longer incubation time (8 h) with 125 and 250 UHMWPE particles/macrophage. Finally, DNA fragmentation (DNA laddering) was observed after 16 h with 125 and 250 particles of Al2O3 per macrophage whereas no laddering was induced by UHMWPE particles even after 24 h incubation. This study shows that although both Al2O3 and UHMWPE particles induce TNF-alpha release, this stimulation was much greater (8-10 times higher) with UHMWPE than Al2O3 (P < 0.05 vs. control). As well, the induction of apoptosis, as measured by activation of caspase-3, PARP cleavage and DNA laddering, is different for these two particles, being faster and more important with Al2O3 than UHMWPE. We hypothesize that the ability of Al2O3 to induce macrophage apoptosis may explain the lower TNF-alpha release observed with these particles and explain the differences seen in osteolysis patterns of ceramic-ceramic (CC) vs. metal-polyethylene (Mpe) articulations. In conclusion, apoptosis may be a major internal mechanism to decrease macrophage activity and may be a desired therapeutic endpoint. The identification of an apoptosis-related pathway in the macrophage response to ceramic particles provides crucial data for a rational approach in the treatment and/or prevention of periprosthetic osteolysis.     

An A2-purinoceptor agonist, NECA, potentiates acetylcholine-induced glucagon secretion.

The effect of a stable structural analogue of adenosine, 5'-N-ethylcarboxamidoadenosine (NECA), was studied on glucagon secretion induced by acetylcholine (ACh) in the isolated perfused pancreas of the newborn dog. The perfusion solution contained a physiological concentration of glucose (4.2 mM). In the first set of experiments, ACh (0.5 microM) infused alone for 10 min induced a significant rise of glucagon secretion (370 +/- 98%, 4 min after the beginning of infusion). In the second set, NECA (2.2 nM) infused 10 min before ACh administration, had no effect per se, but considerably increased the response to ACh (929 +/- 262% of basal value within 3 min). So, the more specific A2 purinoceptor agonist, NECA, potentiated glucagon secretion induced by the cholinoceptor agonist, ACh.     

One year of health and social services for adults 40–50 years old with Down's syndrome

Summary The costs of the public health and social security system supporting adults 40–50 years old with Down's syndrome during one year (1984) have been investigated in the county of Aarhus, representing about 10% of the Danish population. 77% of the probands live in institutions, the rest in private homes or sheltered residences. The average yearly price of an institutionalized adult is DKr. 237,900 =US$ 21,128 = £ 18,174. If the person lives in a private home, the same figures are DKr. 107,239 =US$ 9,524= 8,393. Average for all probands: DKr. 207,587 = US$18,436 = £ 15,858, which is 127% of a skilled worker's salary.     

Induction of protein oxidation by cobalt and chromium ions in human U937 macrophages

Metal particles and ions from hip prostheses have the potential to induce the production of reactive oxygen species (ROS), making them prime suspects for disturbing the cellular balance of oxidants/antioxidants (redox state of the cell). To better understand the cellular effect of metal ions from metal-on-metal prostheses, the aim of this study was to examine the effect of cobalt (Co2+) and chromium (Cr3+) ions on protein oxidation in human U937 macrophages. Protein oxidation was measured by Western blot using antibodies directed against dinitrophenylhydrazine (DNP)-derivatized protein carbonyls, the most commonly measured products of protein oxidation in biological samples. Three DNP-derived proteins were detected. The first has a molecular weight of 16 kDa and is expressed at a very low level. The second has a molecular weight of 48 kDa and its level is not regulated by metal ions. The third is a 69 kDa protein and its level is regulated by Co2+ and Cr3+ ions. Therefore, the last band served as a marker of protein oxidation in the present study. Results showed that Co2+ and Cr3+ ions induced a time- and dose-dependent protein oxidation reaching 6.5 and 2.9 times the control after 72 h, respectively, which were inhibited by the antioxidant glutathione monoethyl-ester. Finally, results showed that the oxidized proteins are mainly found in the cytoplasmic fraction of the cells and are absent from the nucleus. In conclusion, our results suggest that metal ions from metal-on-metal prostheses have the potential to modify the redox state of cells both locally (periprosthetic environment) or systematically (circulating cells). The long term effect of these ions on protein oxidation in vivo remains to be investigated.