Gastrointestinal disorders in Down syndrome

Down syndrome is the most common human chromosomal disorder. Among clinical findings, one constant concern is the high prevalence of gastrointestinal system alterations. The aim of this study was to determine the prevalence of gastrointestinal disorders at a Down syndrome outpatient clinic during a 10‐year follow‐up period. Data from medical files were retrospectively reviewed from 1,207 patients. Gastrointestinal changes occurred in 612 (50.7%). The most prevalent disorder was chronic intestinal constipation. Intestinal parasite occurred in 22% (mainly giardiasis), gastroesophageal reflux disease in 14%, digestive tract malformations occurred in 5%: 13 cases of duodenal atresia, 8 of imperforate anus, 4 annular pancreases, 2 congenital megacolon, 2 esophageal atresias, 2 esophageal compression by anomalous subclavian and 1 case of duodenal membrane. We had 38/1,207 (3.1%) patients with difficulty in sucking and only three with dysphagia that resolved before the second year of life. Peptic ulcer disease, celiac disease, and biliary lithiasis were less prevalent with 3% each. Awareness of the high prevalence of gastrointestinal disorders promotes outstanding clinical follow‐up as well as adequate development and greater quality of life for patients with Down syndrome and their families.     

脊柱三维运动实验加载方式的改进

目的:改进三维运动实验的加载方式。方法:新鲜羊腰椎标本6例(L1~5),置于脊柱三维运动实验机上进行六个自由度的运动。两次预加载后依次对标本进行3、0、0.3Nm的加载,并采集三种加载时的运动图像。3Nm加载及0加载的图像作为传统加载方式计算出脊柱的运动范围及中性区,3Nm加载及0.3Nm加载的图像作为新的加载方式计算出新的脊柱运动范围及中性区,再对两种计算方法得出的运动范围及中性区进行配对t检验,计算两种方法各自的变异率,并进行配对t检验。结果:两种方法得到的运动范围之间不存在差异(P=0.105),但中性区之间存在显著性差异(P=0.013)。采用新的加载方式得到的运动范围的变异系数比以往的方法要小得多(P<0.001)。结论:采用新的加载方式可以得到较为准确的脊柱运动的运动范围。     

Cutis laxa: autosomal dominant inheritance in five generations

Cutis laxa is described in three cases: a 17-year-old man, his mother and his maternal grandmother. The onset of skin symptoms occurred from puberty to early adulthood. The skin was loose-hanging, wrinkled and without elasticity. X-ray examination showed numerous gastrointestinal diverticulae in the two older patients, and both had been operated on for abdominal hernia and genital prolapse. There were no cardiopulmonary symptoms. Histopathological investigation showed a reduction in the amount of elastic tissue in the dermis, but normally localized and ultrastructurally normal components. The family history revealed clinically similar cases in at least five generations, consistent with autosomal dominant inheritance.     

Site-independent prognostic value of chromosome 9q loss in primary gastrointestinal stromal tumours

Although the significance of tumour site for estimating malignant potential in gastrointestinal stromal tumours (GISTs) has recently been recognized, site-specific genetic patterns have not to date been defined. This study examined 52 c-kit-positive primary GISTs (with a mean follow-up of 42.3 months in 51 cases) from three different locations (35 gastric, 12 small intestinal, and five colorectal) using comparative genomic hybridization (CGH). In general, tumour site correlated with key prognostic factors, including tumour size, mitotic rate, proliferative activity, and probable malignant potential. Furthermore, several DNA copy number changes showed a site-dependent pattern. These included losses at 14q (gastric 83%, intestinal 35%; p = 0.001), losses at 22q (gastric 46%, intestinal 82%; p = 0.02), losses at 1p (gastric 23%, intestinal 88%; p = 1 x 10(-5)), losses at 15q (gastric 14%, intestinal 59%; p = 0.002), losses at 9q (gastric 14%, intestinal 53%; p = 0.006), and gains at 5p (gastric 11%, intestinal 53%; p = 0.002). These data demonstrate strong site-dependent genetic heterogeneity in GISTs that may form a basis for subclassification. Prognostic evaluation of DNA copy number changes identified losses at 9q as a site-independent prognostic marker associated with shorter disease-free survival (p = 0.03) and overall survival (p = 0.002). Furthermore, 9q loss also appeared to carry prognostic value in predicting overall survival for patients with advanced or progressive GISTs (p = 0.003).     

CR-lipped bearing is an adequate functional solution to patients with perioperative excessive laxity in cruciate retaining total knee arthroplasty

BackgroundThe cruciate retaining lipped (CR-lipped) bearing is designed to provide more anterior-posterior (AP) stability and could be employed to resolve excessive intraoperative laxity during the cruciate retaining TKA (CR-TKA). The aim of the study was to determine whether the CR-lipped bearing in CR-TKAs with a perioperative excessive laxity allows equivalent functional results as compared to the standard CR articulation.MethodsA cohort of 111 TKAs with CR-lipped bearings was matched to a cohort of conventional CR bearings regarding age and sex. The CR-lipped bearing was used in patients with excessive knee AP laxity and the regular CR bearing was used in patients without excessive AP laxity during TKA. Various PROMs (WOMAC, KSS, SF-36) were assessed preoperatively and at 5-years postoperative in combination with revision rate and Range of Motion (ROM).ResultsPROMs did not differ significantly between both groups 5-years postoperatively. Mean ROM (flexion) 5-years postoperatively was not significantly different. The implant survivorship was 100% for both cohorts with revision for any reason as end point.ConclusionBased on these results, the CR-lipped bearing is a safe and effective solution for mild interoperatively assessed PCL laxity during CR-TKA without loss of function or decreased survivorship at 5 years. Peroperative conversion to a PS-TKA in order to obtain satisfactory functional scores might therefore not be necessary when mild PCL laxity is observed during surgery. Further research should focus on verifying this approach and longer follow-up is needed to generate data on long term survivorship.Level of evidenceLevel IV therapeutic, retrospective, cohort study.     

Epithelioid variant of gastrointestinal stromal tumor: Diagnosis by fine-needle aspiration

Epithelioid gastrointestinal stromal tumors (GISTs) may cause significant diagnostic confusion on fine-needle aspiration (FNA) with carcinomas, neuroendocrine tumors, and melanoma, particularly when metastatic. This study characterizes the cytologic features of nine cases of epithelioid GISTs that were obtained by computerized tomographic guidance in five, by endoscopic ultrasound in three, and from an excised liver tumor in one. Six cases presented as liver masses, one as a perisplenic mass, one as an abdominal mass, and one as a gastric mass. The aspirates revealed mainly single or small clusters of epithelioid cells with a moderate amount of granular to clear cytoplasm, small uniform nuclei with mild to marked nuclear envelope irregularities. Binucleation and intranuclear inclusions were frequent findings. Collagenous stroma was seen in most cases. In three cases, a neuroendocrine tumor was the initial diagnosis. Immunocytochemical staining for c-kit (CD117) was performed on cellblocks in six cases and was positive in five cases. On the subsequent surgical specimen, CD117 was positive in the c-kit-negative cytology case. The diagnosis of GIST should be considered in aspirates of the gastrointestinal tract, liver, mesentery, or abdominal wall mass lesions when epithelioid cells are the predominant cell type. Ancillary studies such as immunohistochemical stains are usually helpful in making a definitive diagnosis.     

Role of vestibular and neck inputs for the perception of object motion in space

Summary The contribution of vestibular and neck inputs to the perception of visual object motion in space was studied in the absence of a visual background (in the dark) in normal human subjects (Ss). Measures of these contributions were obtained by means of a closed loop nulling procedure; Ss fixed their eyes on a luminous spot (object) and nulled its actual or apparent motion in space during head rotation in space (vestibular stimulus) and/ or trunk rotation relative to the head (neck stimulus) with the help of a joystick. Vestibular and neck contributions were expressed in terms of gain and phase with respect to the visuo-oculomotor/joystick feedback loop which was assumed to have almost ideal transfer characteristics. The stimuli were applied as sinusoidal rotations in the horizontal plane (f= 0.025–0.8 Hz; peak angular displacements, 1–16°). Results: (1) During vestibular stimulation, Ss perceived the object, when kept in fixed alignment with the moving body, as moving in space. However, they underestimated the object motion; the gain was only about 0.7 at 0.2–0.8 Hz and clearly decreased at lower stimulus frequencies, while the phase exhibited a small lead. (2) During pure neck stimulation (trunk rotating relative to the stationary head), the object, when stationary, appeared to move in space counter to the trunk excursion. This neck-contingent object motion illusion was small at 0.2–0.8 Hz, but increased considerably with decreasing frequency, while its phase developed a small lag. (3) Vestibular, neck, and visuo-oculomotor effects summed linearly during combined stimulations. (4) The erroneous vestibular and neck contributions to the object motion perception were complementary to each other, and the perception became about veridical (G1, 0°), when both inputs were combined during head rotation with the trunk stationary. The results are simulated by an extended version of a computer model that previously had been developed to describe vestibular and neck effects on human perception of head motion in space. In the model, the perception of object motion in space is derived from the superposition of three signals, representing object to head, (visuo-oculomotor; head coordinates), head on trunk (neck; trunk coordinates), and trunk in space (vestibular-neck interaction; space coordinates).Supported by Deutsche Forschungsgemeinschaft, SFB 325     

Loss of mucosal CD4 lymphocytes is an early feature of HIV infection.

T cell subsets in the gut mucosa are distinct populations and their imbalance in HIV has specific implications in infection. Alterations in T cell subsets in duodenal biopsies were investigated in 17 asymptomatic HIV patients, 24 AIDS patients and 10 controls with non-ulcer dyspepsia. Immunohistochemistry and immunofluorescence using MoAbs to CD3, CD4, CD8, CD68, CD45RA, CD45RO and gp120 were performed on frozen sections. In the lamina propria, there was a significant depletion of CD4+ cells at all stages of HIV, but the density of CD8 lamina propria cells was increased. Intraepithelial lymphocytes were decreased in AIDS patients. There was a significant correlation between cellular density and mucosal CD3+ lymphocytes, and between mucosal CD3+ and CD8+ lymphocytes. Although mucosal CD4,CD45RO+ 'memory' cells were decreased, CD8,CD45RO+ 'memory' cells were increased. Mucosal CD4+ lymphocyte depletion occurred early in HIV, and thus their role in mucosal protection against opportunistic infection should be revised. Mucosal CD8+ lymphocytes initially increased, but decreased when CD4 blood counts were depleted, perhaps contributing to loss of host protection against infection. Intraepithelial lymphocyte depletion may also contribute to opportunistic infection.     

p53 expression in gastrointestinal stromal tumors

The understanding of gastrointestinal stromal tumors (GIST) is complex because of their divergent differentiation and unpredictable behavior. However, our understanding is becoming clearer, despite some cases of tumors which are exceptions from the typical cases. Tumor size, mitotic rate and, to a lesser degree, location, are the most important predictive parameters for the behavior of GIST. In this study, expression of p53 protein was evaluated in 15 cases of GIST. Tumors were divided into three groups: (i) benign (mitotic index [MI] < 5/50 high-power fields [HPF] and size < 5 cm); (ii) borderline (MI < 5/50 HPF and size > or = 5 cm); and (iii) malignant (MI > or = 5/50 HPF, irrespective of size). The mean values of p53 expression in the three groups were significantly different (benign, 10.6%; borderline, 33.8%; and malignant, 71%). The conclusion of the present study is that p53 overexpression correlates well with the malignant potential of GIST.     

Gastric fibromyxoma, a distinct entity of pure fibroblastic tumor--an ultrastructural study

A rare case of fibromyxoma arising in the stomach of a 78-year-old male is presented. A well-defined, encapsulated tumor measuring 27x17x8 cm showed a lobular growth in the submucosa and muscularis propria, with no association with the propria mucosa. Histologically, the tumor was characterized by a diffuse, widely spaced proliferation of small spindle, stellate and round cells with dendritic outlines with fibromyxoid stroma. Neither cellular atypia nor mitotic figures were observed. Immunohistochemically, the tumor was positive for vimentin and CD34 but negative for CD117, alpha-smooth muscle actin, muscle actin, desmin and S-100 protein. Ultrastructurally, the tumor cells had irregularly shaped nuclei and cytoplasm containing moderate amounts of mitochondria, rough endoplasmic reticulum, subplasmalemmal densities, and short interdigitating processes. These findings indicated the fibroblastic nature of the tumor. The patient was well without recurrence 20 months after surgery. It is important to recognize that gastric fibromyxoma is a distinct entity and to include it in the differential diagnosis of gastric mesenchymal tumors, as the tumors show a different clinical behavior and as limited surgery with local excision is possible.