Syh-Jae Lin

Sonographic Features Related to Volvulus in Neonatal Intestinal Malrotation

This 3 year prospective study evaluated the sensitivity and specificity of abdominal ultrasonography and color Doppler ultrasonography in 31 neonates with suspected malrotation or malrotation with volvulus. Water instillation was used to detect duodenal dilatation, edema, and malrotated bowels. Twenty patients with ultrasonographic characteristics of inversion of the superior mesenteric artery and superior mesenteric vein were later surgically proved to have malrotation. Nine of these 20 patients also had volvulus. Sonographic features suggestive of volvulus included duodenal dilation with tapering configuration (8 of 9 cases, 89%), fixed midline bowel (8 of 9 cases, 89%), whirlpool sign (8 of 9 cases, 89%), and dilation of the distal superior mesenteric vein (5 of 5 cases, 100%). The sensitivity and specificity of duodenal dilation with tapering configuration for detecting volvulus were 89% and 92%, respectively; of fixed midline bowel, 89% and 92%; of whirlpool sign, 89% and 92%; and of dilation of distal superior mesenteric vein, 56% and 73%. The results of this study indicate that ultrasonographic features of inversion of the superior mesenteric artery and superior mesenteric vein could aid in the diagnosis of malrotation, and certain sonographic features can also be used to evaluate volvulus, a condition requiring emergent operation.

Factors related to detection of blood flow by color Doppler ultrasonography in intussusception

Color Doppler ultrasonography was performed in 125 patients with 134 intussusceptions. Color flow was present in 121 cases of intussusception (group A) and was absent in 13 cases (group B). Young age and duration of symptoms greater than 48 hr were significantly related to the nonvisualization of blood flow detected by color Doppler sonography (P < 0.05). The successful rate of air reduction was significantly higher in group A than in group B (109 of 121 versus 4 of 13). Color Doppler ultrasonography is useful to predict the reducibility of an intussuscepted intestine. The nonvisualization of blood flow by this method is not a contraindication for air reduction.

PFAPA SYNDROME (PERIODIC FEVER, APHTHOUS STOMATITIS, PHARYNGITIS, ADENITIS)

Abstract: This paper aims to remind paediatric clinicians to suspect and confirm ‘PFAPA’ syndrome (Periodic Fever, Aphthous stomatitis, Pharyngitis and cervical Adenitis syndrome). We report two cases of PFAPA syndrome: a 3-year-old healthy boy with atopic rhinitis and a boy aged 8 years 5 months who simultaneously had lymphocytic vasculitis syndrome treated with immunosuppressive drugs. Both met Marshall’s criteria. The literature regarding PFAPA syndrome was complied using a Medline search for articles published between 1963 and 1998 and we then reviewed the reference lists of the articles. The Medline search revealed 28 cases with available clinical manifestations, management and prognosis. Our study describes two additional cases. We divided the cases into typical (28 cases) and atypical (two cases) PFAPA syndrome. In typical PFAPA, the age of onset was less than 5 years in most cases and the patients presented 4.9 ± 1.4 days of fever (100%), pharyngitis (89.3%), cervical adenitis (72.1%), stomatitis (71.4%), malaise (64.3%), headache (60.7%), abdominal pain (53.6%) and nausea/vomiting (17.9%). Afebrile intervals were 3.2 ± 2.4 months and increased with age. The time from initial onset to final episode was 3 years 7 months ± 3 years 6 months. The total number of episodes was 8.3 ± 2.5 (range 6–14). Effective treatment included steroids, tonsillectomy/adenoidectomy and cimetidine. The general outcome was good. In atypical PFAPF, the clinical manifestations were similar to those of typical PFAPA except that the age of onset was more than 5 years, and life-threatening intestinal perforation happened once in a patient with underlying Fanconi’s anaemia. It was concluded that typical PFAPA syndrome is benign and can be diagnosed by detailed history-taking and from physical findings during repeated febrile episodes with tests to rule out other periodic fever syndromes. A review of the literatures since the first report in 1987 has shown that typical PFAPA syndrome is not associated with significant long-term sequelae and has a good response to steroids. One patient with atypical PFAPA, who received low-dose steroids for over 1 year, developed intestinal perforation after an increment of the 7-day steroid dose. If an underlying problem requires long-term immunosuppressive medication, it is wiser to choose cimetidine rather than increasing the steroid dosage to resolve atypical PFAPA.

Sonographic evaluation of the pancreatic duct in normal children and children with pancreatitis

We investigated the diameter of pancreatic duct using ultrasonography in 51 children with pancreatitis and age‐matched healthy control children over a 5 year period. The diameters of pancreatic duct and pancreatic body were measured simultaneously by sonography. The mean ages of children with acute pancreatitis and chronic pancreatitis were 9.7 +/‐ 3.9 and 10.3 +/‐ 3.1 years, respectively (range, 1 to 8 years). The mean age of normal children was 9.6 +/‐ 5.3 years. A significant difference was found in diameter of the pancreatic duct between children with acute and chronic pancreatitis versus that of age‐matched control. In addition, a significant difference in diameter of the pancreatic body was found between children with acute pancreatitis and age‐matched controls, but there was no marked difference in diameter of the pancreatic body between normal persons and those with chronic pancreatitis. The mean diameters of the pancreatic duct in acute pancreatitis and chronic pancreatitis were 2.34 +/‐ 0.47 mm and 2.84 +/‐ 0.67 mm, respectively, which was greater than that of normal children (1.65 +/‐ 0.45 mm). Pancreatic ducts with diameters greater than 1.5 mm in children between 1 and 6 years, greater than 1.9 mm at ages 7 to 12 years, or greater than 2.2 mm at ages 13 to 18 years were significantly associated with the presence of acute pancreatitis. Thirty‐two patients, including 25 with acute pancreatitis and 7 with chronic pancreatitis, underwent follow‐up measurement of pancreatic duct and serum lipase examination on at least three occasions. A good correlation between the diameter of pancreatic duct and serum lipase level was found. Thus, ultrasonography of the pancreatic duct is valuable in diagnosis and monitoring of pancreatitis in children.

Evaluation of cytotoxic function and apoptosis in interleukin (IL)-12/IL-15-treated umbilical cord or adult peripheral blood natural killer cells by a propidium-iodide based flow cytometry

Both deficient natural killer (NK) cell effector function and increased propensity to apoptosis of neonatal NK cells contribute to the increased susceptibility to infection in the neonates. Interleukin (IL)‐12 and IL‐15 are two immunoregulatory cytokines known to enhance cytolytic function of neonatal NK cells. The present study aims to simultaneously investigate the effect of IL‐12/IL‐15 on K562 cytotoxicity as well as NK cells apoptosis of enriched umbilical cord blood (CB) and adult peripheral blood (APB) NK cells, using flow cytometric cytotoxicity assays. The results indicated that (i) prior to cytotoxicity assays, CB NK cells underwent greater degree of spontaneous apoptosis than did APB NK cells; (ii) both IL‐12 and IL‐15 inhibited the spontaneous apoptosis of CB NK cells, while IL‐15 promoted the apoptosis in APB NK cells; (iii) the deficient K562 cytotoxicity of CB NK cells could be enhanced to levels comparable with that of APB NK cells by IL‐15; (iv) IL‐15 increased the percentages of apoptosis in NK–K562 conjugates in a dose‐dependant manner in both CB and APB with a greater effect seen with APB NK cells; (v) target‐induced apoptosis was observed with APB NK cells which were further enhanced with IL‐15. However, CB NK cells, unstimulated or IL‐15‐activated, were resistant to K562‐induced apoptosis. Thus, the multi‐parameter flow cytometry analysis not only demonstrates better for the deficient CB NK function but also provides greater details for cytotoxic mechanisms of NK cells.

Distribution, Infections, Treatments and Molecular Analysis in a Large Cohort of Patients with Primary Immunodeficiency Diseases (PIDs) in Taiwan

One hundred and twenty-four patients (from 120 families) diagnosed as primary immunodeficiency diseases were enrolled from five tertiary medical centers. The distribution by an update eight categories showed 45 patients (13 females/32 males; 36.3%) with “predominant antibody deficiencies,” 27 patients (6/21; 21.8%) with “T- and B-cell immunodeficiency,” 25 patients (9/16; 20.2%) with “congenital defects of phagocyte,” 25 patients (4/21; 20.2%) with “other well-defined immunodeficiency syndromes,” one boy (0.8%) with “disease in immune deregulation” (Chediak-Higashi syndrome) and another with “complement 3 deficiency.” None had “defects in innate immunity” or “auto inflammatory disorders.” Pseudomonas and Salmonella spp. were the two most identified microorganisms in septicemia (39.7%; 27/68 episodes). Twenty-three patients (18.5%) had mortality. Stem cell transplantation succeeded in 7 of 12 patients. In addition to nine patients with DiGerge syndrome recognized by FISH, direct sequencing identified 12 unique mutations from 20 families, reflecting distinct Taiwan geography, although a selection bias may exist.

Hodgkin's Disease in a Child with Hyperimmunoglobulin E Syndrome

A 10-year-old boy with hyperimmunoglobulin E (HIE) syndrome was admitted to the hospital due to intermittent fever and a growing neck mass noted for 3 months. He had had chronic eczema and recurrent skin infections since infancy. At age 8, the diagnosis of HIE was established when a pneumatocele was found in the presence of extremely elevated serum IgE levels (7842 IU/mL). He also had defective T-lymphocyte function, manifested by cutaneus anergy, as well as abnormal proliferative response to mitogenic stimuli. Chemotactic function of neutrophils was normal. Pathological examination of the lymph node disclosed Hodgkins disease (nodular sclerosis). A high index of suspicion for lymphoma should be given in patients with HIE syndrome who present with lymph node enlargement.

The regulatory function of umbilical cord blood CD4(+) CD25(+) T cells stimulated with anti-CD3/anti-CD28 and exogenous interleukin (IL)-2 or IL-15.

The abundance of CD4+ CD25+ regulatory T cells in umbilical cord blood (UCB) might contribute to the decreased severity of graft‐vs.‐host disease (GVHD) for UCB transplantation. This study aims to characterize the phenotypes and suppressive function of UCB CD4+ CD25+ T cells under the influence of anti‐CD3/anti‐CD28 (CD3/CD28) and exogenous interleukin (IL)‐2 or IL‐15. Higher percentages of CD4+ CD25high and FoxP3+ cells were detected in UCB compared to their adult counterparts. IL‐15 was as effective as IL‐2 in enhancing the proliferation of CD3/CD28 stimulated UCB CD4+ CD25+ T cells. Phenotypically, IL‐2/IL‐15‐stimulated UCB CD4+ CD25+ T cells expressed higher level of CTLA‐4, GITR, membrane bound transforming growth factor‐β (mTGF‐β), and especially Foxp‐3 than controls. IL‐2/IL‐15‐stimulated UCB CD4+ CD25+ T cells also produced much higher IL‐10 and TGF‐β than controls; while IL‐2/IL‐15‐stimulated UCB CD4+ CD25− T cells showed increased TGF‐β, but not IL‐10 production. IL‐2/IL‐15‐cultured UCB CD4+ CD25+ T cells showed comparable suppressor activity on allogeneic adult CD4+ T‐cell proliferation compared to controls, partly through a contact‐dependent fashion. Taken together, IL‐2/IL‐15‐stimulated UCB CD4+ CD25+ T cells show distinct regulatory T‐cell phenotypic and functional features, and may be applied for the alleviation of GVHD severity following UCB transplantation.

The effect of interleukin-12 and interleukin-15 on CD69 expression of T-lymphocytes and natural killer cells from umbilical cord blood.

We investigated the effect of two immunoregulatory cytokines interleukin-12 (IL-12) and IL-15, alone or in combination, on CD69 expression of mononuclear cells (MNCs) obtained from umbilical cord blood (CB) and adult peripheral blood (APB). We established that (1) CD3/69, but not CD16/69, expression on CB MNCs could be increased with IL-12, IL-15 or both in 18-hour cultures, but to a lesser degree compared to that on corresponding APB MNCs, (2) CD3/69 expression on CB MNCs was significantly increased after 1 week’s culture with IL-12, especially with IL-15, exceeding that on APB MNCs similarly activated and (3) CD16/69 expression on CB MNCs, but not APB MNCs, was greatly increased after 1 week’s culture with IL-15. The combination of IL-12 + IL-15 resulted in greater CB CD3/69 expression than individual cytokines, while producing less of an effect on CD16/CD69 expression as compared to IL-15 alone. The results of our study indicate that neonatal T and NK cells readily respond to cytokine stimulation by upregulating CD69 expression, with a greater effect achieved using IL-15 compared to IL-12.

Different articular outcomes of Still's disease in Chinese children and adults.

Abstract: The clinical manifestations, treatment and course, and articular outcomes of 24 children with juvenile-onset Still’s disease (JOSD) and 21 adults with adult-onset Still’s disease (AOSD) were compared retrospectively. There was no significant difference in the initial clinical and laboratory manifestations except that more adults presented with a sore throat (81% vs 46%, p = 0.03). Although serum ferritin was almost always elevated in both diseases, adults had significantly higher serum ferritin concentrations compared with those of children. Steroid treatment was required in 71% of children and 52% of adults, while disease-modifying antirheumatic drugs were used in 42% of children and 24% of adults during the course. Chronic arthritis (>6 months) occurred in comparable proportions of patients with JOSD and AOSD (46% vs 38%, p = 0.82), irrespective of the disease pattern (monocyclic or polycyclic). However, severe deforming arthritis with marked functional limitation occurred only in JOSD, particularly with polyarthritis at disease onset (more than five affected joints). In contrast, AOSD patients with chronic arthritis had a favourable functional outcome at the end of the follow-up. Our study suggested different articular outcomes of Still’s disease in Chinese children and adults.