Social isolation in mice: behavior, immunity, and tumor growth.

The aim of this study was to investigate the behavioral, immunological, and neurological effects of long-term isolation in an animal model. Male C3H/eB mice wereraised in either social isolation or standard conditions for 6 weeks. At 10 weeks, each group was further divided into 3 sets. (A) Physical strength and behavior were evaluated with the grip strength, hot plate, staircase, and elevated plus-maze tests. Natural-killer cell activity and lymphocyte proliferation were measured. (B) Half the animals were subjected to electric shock with 3 reminders, and freezing time was evaluated at each reminder. Cortisone levels were evaluated after 16 weeks. (C)Mice were injected with 38 C-13 B lymphoma cells and followed for tumor size and survival. Strength evaluation yielded asignificantly lower body weight and grip strength in the socially isolated mice. Behavioral test results were similar in the two groups. The pattern of reactions to stress conditioning differed significantly, with the socially isolated mice showing an incline in freezing with each successive reminder, and the control mice showing a decline. The socially isolated mice had significantly attenuated tumor growth, with no significant difference in survival from control mice. There were no significant between-group differences in immunological parameters. In conclusion, social isolation serves as a model for chronic stress. It was associated with significant changes in stress conditioning reaction, resembling symptoms of post-traumatic stress disorder, and attenuated tumor development. No differences from controls were found in behavior tests, immune parameters, or survival after tumor cell inoculation.Lay summaryThis article explores biological and behavioral consequences of social isolation in a mice model. Our results show that social isolation leads to changes in the Hypothalamic-hypophyseal-adrenal axis, which in turn alter the response to stress. Additionally, social isolation was shown to impact tumor progression.

Secondary bacteremia following adenovirus infection.

Adenovirus is a common pediatric pathogen responsible for a wide variety of infections. Despite this, secondary bacteremia following an adenovirus infection has not been previously systematically described. Herein, we describe seven cases of secondary bacteremia following an adenovirus infection in hospitalized children during an 8-year period. Pediatricians should be informed of this serious complication.

Pediatric otogenic sigmoid sinus thrombosis: 12-Year experience.

OBJECTIVES: Otogenic sigmoid sinus thrombosis is a rare complication of acute otitis media. Treatment remains controversial particularly regarding extent of surgical intervention. The aim of the study was to review the 12-year experience of a major medical center with the treatment of sigmoid sinus thrombosis in children. METHODS: Retrospective case series identified by database review in a tertiary university-affiliated pediatric medical center. Twenty-four children aged 7-155 months were treated for sigmoid sinus thrombosis from 2000 through 2011. RESULTS: The transverse sinus was also involved in 10 patients, and the jugular vein, in 4. Acute otitis media with mastoiditis was the causative factor in all cases. Subperiosteal abscess was diagnosed in 21 patients, 11 with epidural involvement. Treatment in all cases consisted of broad-spectrum antibiotics and ventilation tube insertion. Twenty-one children (87.5%) underwent mastoidectomy with removal of bone covering the sigmoid sinus to drain pus and remove granulations from the epidural cavity, without aspiration or sinus drainage. Twenty-two patients received low-molecular-weight heparin for 3-6 months postoperatively. Children infected with Fusobacterium necrophorum had a longer and more severe course with coexisting osteomyelitis. There were no neurologic sequelae or hematologic complications. Follow-up imaging, performed in 15 children, revealed partial or full recanalization in 87%. CONCLUSIONS: Relatively conservative surgical intervention appears to yield good results in children with sigmoid sinus thrombosis consequent to acute otitis media. Anticoagulants are safe if correctly administered and may prevent extension of the thrombus.

Age and duration of bleeding symptoms at diagnosis best predict resolution of childhood immune thrombocytopenia at 3, 6, and 12 months.

OBJECTIVE: To evaluate the predictive value of clinical features at diagnosis of immune thrombocytopenia (ITP) for resolution of disease. STUDY DESIGN: Hospital records of 472 consecutive children (<18 years old) with ITP cared for at 2 participating centers were reviewed retrospectively and data related to the initial presentation were recorded. Logistic regression analysis was used for calculating prediction of resolution at 3, 6, and 12 months from diagnosis. RESULTS: The most significant predictors for resolution of ITP at 3, 6, and 12 months were age at onset <10 years and abrupt onset (history of <2 weeks of bleeding). We designed a prediction rule for ITP chronicity based on these criteria. The rate of developing chronic ITP for low, intermediate, and high risk children at diagnosis of ITP was 11%, 39%, and 63%, respectively. Recovery rate at 3 months for low, intermediate, and high risk children was 72%, 43% and 30%, respectively. CONCLUSIONS: We present a simple rule to predict recovery from ITP at 3, 6, and 12 months from diagnosis. For prediction of resolution at 3 months, our rule was in agreement with the more complex, previously described Nordic score. Prediction of resolution of ITP may enable practitioners to better inform children and parents at the time of diagnosis, resulting in reduced anxiety and improved quality of life.

Clinical and histopathologic spectrum of alopecia mucinosa/follicular mucinosis and its natural history in children.

BACKGROUND: Some authorities consider alopecia mucinosa (AM)/follicular mucinosis (FM) to invariably represent mycosis fungoides (MF). This understanding of AM/FM derives from observations in adults. OBJECTIVES: We sought to explore the clinicopathologic features and natural history of pediatric AM/FM. METHODS: Medical records were searched for children given the diagnosis of AM/FM from 1998 through 2009. Diagnosis of AM/FM was defined as the presence of well-demarcated hairless plaques with follicular prominence plus an abundance of mucin on histopathologic examination. RESULTS: Forty children with a clinical diagnosis of AM/FM were identified. Nine did not meet the inclusion criteria. In the 31 remaining cases (16 boys, 15 girls) the mean age at onset was 9 ± 3.5 years. Histopathologic examination showed folliculotropism in 28 patients (90%) and epidermotropism in 15 (48%). Twelve cases fulfilled the International Society of Cutaneous Lymphomas (ISCL) diagnostic criteria for early MF. The histopathologic findings were typical of MF in only in two of these cases. T-cell receptor gene rearrangement was positive in 3 of 6 (50%) of tested samples, one in a patient who fulfilled the ISCL criteria for early MF. Mean duration of follow-up was 6.2 ± 3.7 years. All skin lesions resolved and none persisted or recurred. Hodgkin lymphoma was diagnosed 6 months after diagnosis of AM/FM in one patient. LIMITATIONS: This was a retrospective study. CONCLUSIONS: Although some pediatric cases meet the diagnostic criteria for MF, AM/FM cannot be regarded unequivocally as early follicular MF in this age group. We suggest the current diagnostic criteria for early MF should exclude children with AM/FM. Long-term follow-up of children with AM/FM is nevertheless warranted.

Three sibs with microcephaly, clubfeet and agenesis of corpus callosum: a new genetic syndrome?

Clubfoot is a common birth deformity, and agenesis of the corpus callosum is one of the most prevalent brain malformations. We describe three sibs of Arab origin, who were born with clubfeet, agenesis of corpus callosum, and minor anomalies. Two of them were born with microcephaly. This phenotype may represent a novel autosomal recessive genetic condition.

An emerging 1q21.1 deletion-associated neurodevelopmental phenotype.

In this study, we describe the neurodevelopmental and epileptic phenotypes in a family with an inherited 1q21.1 deletion. During the pregnancy with the proband, increased nuchal translucency and oligohydramnion were detected. The proband showed mild global developmental delay and ataxic gait. Seizures started in the proband at the age of 2 years and manifested as generalized tonic-clonic seizures, atypical absence seizures, head drops, and drop attacks with no abnormal findings on interictal electroencephalogram. We performed an Agilent Human Genome CGH (comparative genomic hybridization) Microarray 105A, and a microdeletion on chromosome 1q21.1 was identified in both the patient and his asymptomatic father. This deletion encompasses 1.65 Mb and is larger than the reported recurrent class I deletions in this region. Cryptic cytogenetic abnormalities should be considered in patients with neurodevelopmental problems and atypical presentation of epilepsy with a normal electroencephalography (EEG).

Selective IgA deficiency in children in Israel.

IgA deficiency is the most common human primary immune-deficiency. We evaluated the clinical and immunological characteristics of selective IgA deficiency in children in Israel. The study group included 63 children diagnosed with IgA deficiency from 1987 to 2005. Mean follow-up time per child was 10.6 years. Average age at diagnosis was 10.5 years. In one child, the IgA deficiency was transient. Infectious diseases, mainly recurrent pneumonia and ear infection, were common and occurred in 25 patients (39.7%). Allergic diseases were documented in 20 (31.7%) of our patients. Thirteen children (20.6%) had autoimmune diseases. Malignancies were diagnosed in three children (4.8%), an association that has not been reported in previous series. IgA deficiency appears to be a risk factor for infections, allergic diseases, autoimmune conditions, and malignancy.

Autosomal dominant syndrome of mental retardation, hypotelorism, and cleft palate resembling Schilbach-Rott syndrome.

We present a family segregating for an autosomal dominant syndrome of hypotelorism, cleft palate/uvula, high-arched palate and mild mental retardation. Although these findings may suggest a form of holoprosencephaly, no holoprosencephaly was found on MRI of the proposita. Results of genetic studies were normal including FISH for deletion of 22q11, karyotype analysis, fragile X testing, high-resolution comparative genomic hybridization and SEPT9, SHH mutation analysis. The syndrome is reminiscent of the infrequently recognized autosomal dominant Schilbach-Rott syndrome.

Acute cerebellitis presenting as tonsillar herniation and hydrocephalus.

Acute cerebellitis is a rare inflammatory syndrome, often characterized by cerebellar dysfunction of rapid onset. We describe two children, a girl aged 5 years and a boy aged 11 years, with acute cerebellitis. Both manifested tonsillar herniation and hydrocephalus. The cause was Mycoplasma pneumoniae infection in the first patient, and unknown in the second. The girl was treated conservatively with steroids and diuretics, as well as vibramycin, and the boy required insertion of a ventriculostomy. Both presented a good prognosis and full recovery.

Autosomal dominant isolated question mark ear.

Question mark (Cosman) ear is an auricular abnormality characterized by a cleft between the lobule and the lower part of the helix, sometimes accompanied by a prominent or deficient upper part of the helix, shallow skin dimple on the posterior surface of the ear, or transposition of the ear lobe/antitragus. It can be inherited as an autosomal dominant trait. Only two families with more than one member with Question mark ear have been reported previously. Here we report on a female infant with bilateral isolated Question mark ear. The family history revealed a similar abnormality in her father and paternal grandfather. The similarity of the Question mark ear to the ear abnormalities described in auriculo-condylar syndrome (ACS) is discussed.

Systemic allergic reaction to tree processionary caterpillar in children.

Contact with the tree processionary caterpillar or ingestion/inhalation of its airborne toxin-containing hairs and spines may cause a direct histamine-releasing or IgE-mediated allergic reaction in humans. The most common manifestations are urticaria and dermatitis; systemic manifestations such as respiratory involvement and anaphylaxis have been reported mainly in foresters. We describe a 12-year-old child who was presented to the emergency department with systemic allergic reaction (pruritic rash, conjunctival hyperemia, dyspnea, and wheezing), which eventually proved to be due to exposure to the pine tree processionary caterpillar. The diagnosis was made only after the child's repeated exposure to the caterpillar. Tree processionary caterpillar should be added to the list of causes of systemic allergic reactions in children, especially in endemic areas, and medical staff should be alerted the range of clinical manifestations to ensure prompt diagnosis and treatment.

Recurrent parotitis in selective IgA deficiency.

Recurrent parotitis is an uncommon condition in children. In most cases the etiology is unknown, although the disease is occasionally associated with viral infections, autoimmune disorders and immunodeficiency. We describe, for the first time, a child with recurrent parotitis and isolated immunoglobulin A (IgA) deficiency, without autoimmune disease. As IgA is the main immunoglobulin secreted into the mucosal surfaces, including that of the respiratory and gastrointestinal tracts, and into the saliva, the lack of IgA may be involved in the pathogenesis of recurrent parotitis. We recommend that IgA and other immunoglobulins be tested in all cases of recurrent parotitis.