[18F]FDG-PET Evaluation of Spinal Pathology in Patients in Oncology: Pearls and Pitfalls for the Neuroradiologist.

[18F]FDG-PET is a widely used technique for specific evaluation of disease and treatment response in oncology. However, the principles behind [18F]FDG-PET imaging allow a wide-ranging array of benign and malignant pathologies to be identified on both initial and routine surveillance imaging. This is important for clinicians and radiologists, alike, in that effective and accurate evaluation of malignancy and metastatic disease, specifically involving the spine and central nervous system, is crucial. In this article, we review the normal and posttherapy appearance of the spine on [18F]FDG-PET, the various types and patterns of metastatic disease that involve the spine and spinal cord, and, finally, important spinal pathologies that may mimic malignancy on [18F]FDG-PET.

Mitochondrial basis for immune deficiency. Evidence from purine nucleoside phosphorylase-deficient mice.

We generated purine nucleoside phosphorylase (PNP)-deficient mice to gain insight into the mechanism of immune deficiency disease associated with PNP deficiency in humans. Similar to the human disease, PNP deficiency in mice causes an immunodeficiency that affects T lymphocytes more severely than B lymphocytes. PNP knockout mice exhibit impaired thymocyte differentiation, reduced mitogenic and allogeneic responses, and decreased numbers of maturing thymocytes and peripheral T cells. T lymphocytes of PNP-deficient mice exhibit increased apoptosis in vivo and higher sensitivity to gamma irradiation in vitro. We propose that the immune deficiency in PNP deficiency is a result of inhibition of mitochondrial DNA repair due to the accumulation of dGTP in the mitochondria. The end result is increased sensitivity of T cells to spontaneous mitochondrial DNA damage, leading to T cell depletion by apoptosis.

Strategy for increasing detection rates of drug and alcohol abuse in paediatric emergency departments.

AIM: To determine whether implementation of criteria for performing a toxicology screen and increasing staff awareness improve detection of substance abuse among adolescents presenting to the emergency department. METHODS: Patients 12 to 18 years of age presenting to one of three emergency departments in Israel were included in a prospective cohort study. In the 'study' hospital, a set of criteria for urine toxicology screen and measurements of ethanol serum level were implemented. No specific interventions were implemented in the two other hospitals. The main outcome measure was the rate of substance abuse detection. RESULTS: The number of adolescents seen in the participating centres was 3200 at the study hospital, and 3493 and 2792 at the two other hospitals. High blood ethanol concentrations were found in 49 patients at the study hospital compared with 30 and 19 patients at the two other hospitals (p < 0.001). Illicit drugs were detected in 13, 4 and 1 patients, respectively (p = 0.002). CONCLUSIONS: Introducing structured guidelines for ordering toxicological screening increases the detection of alcohol and drug of abuse among adolescents presenting to paediatric emergency departments.

The role of gut microbiome in the pathogenesis of psoriasis and the therapeutic effects of probiotics.

The adult intestine hosts a huge number of diverse bacterial species, collectively referred to as the microbiome, that reside mainly in the lower gut, where they maintain a symbiotic relationship with their host. Recent research points to a central role of the microbiome in many biological processes. These microbial communities are influenced by multiple environmental and dietary factors and can modulate immune responses. In addition to local effects on the gastrointestinal tract, the microbiota is associated with effects on other organs and tissues, such as the skin. Indeed, an altered microbiome has been associated with skin disorders in several instances. Thus, in this review, we describe the recent advances regarding the interplay between gut microbiota and the skin. We explore how this potential link affects skin homeostasis and its influence on modulating the cutaneous immune response, focusing on psoriasis disorder. Finally, we discuss how to take advantage of this interplay to manage this disorder, particularly through probiotics administration. In the gastrointestinal tract, the microbiome has been proven to be important in the maintenance of the balance between effector T cells and regulatory T cells, and the induction of immunoglobulin A. Moreover, gut bacterial dysbiosis is associated with chronic inflammatory disorders of the skin, such as psoriasis. Thus, the microbiome can be considered an effective therapeutical target for treating this disorder. Despite some limitations, interventions with probiotics seem promising for the development of a preventive therapy by restoring altered microbiome functionality or as an adjuvant in specific immunotherapy.

Quantifying the Levels of Knowledge, Attitude, and Practice Associated with Sickle Cell Disease and Premarital Genetic Counseling in 350 Saudi Adults.

Our study aims to observe the levels of knowledge, attitude, and practice (KAP) associated with sickle cell disease (SCD) and premarital genetic counseling (PMGC) in 351 Saudi adults. The relationships between KAP levels and sociodemographic characteristics (age, gender, marital status, and educational level) were observed. The study was conducted in King Khalid University Hospital between February 21, 2017, and March 7, 2018. A total of 351 Saudi participants attending the primary care clinic were selected using convenience sampling and were given a self-administered questionnaire. Overall, the 351 participants had the best attitude (41% scoring "good"), followed by knowledge (28.8%), and, lastly, practice (19.1%). Out of the sociodemographic characteristics, age group was the most statistically significant in all the three categories (knowledge, attitude, and practice). The > 50-year age group performed the worst in all the three categories. Despite the advancements in public healthcare measures in Saudi Arabia, our study revealed that there are still many gaps to be filled regarding the knowledge, attitude, and practice associated with SCD and PMGC.

The outcome of management of "troublesome" vs "non-troublesome" phalangeal neck fractures in children less than 2 years of age.

BACKGROUND: Several authors have indicated that there are specific poor prognostic factors which may affect the outcome of management of phalangeal neck fractures. In the authors' centre, phalangeal neck fractures with any of these poor prognostic factors are labelled "troublesome". Any of the following five criteria will qualify the fracture to be regarded as "troublesome": concurrent vascular compromise of the fractured digit, open/partial amputation injuries, comminution of the fractured phalangeal head, concurrent epiphyseal or juxta-epiphyseal fractures distal to the fractured phalangeal head, and all Type III fractures (as per Al-Qattan classification). METHODS: The effect of these poor prognostic factors has not been investigated in the youngest paediatric age group; the hands of whom are known to be most forgiving. The purpose of this study is to compare the outcome of management of seven "troublesome" vs nine "non-troublesome" phalangeal neck fractures in children less than 2 years of age. Demographic data (age, sex, fracture site/type, and troublesome factors) were reviewed for the 16 cases. All patients were treated according to a specific protocol, and the outcome was documented using a modified Al-Qattan's outcome grading system. RESULTS: Of the nine children with non-troublesome fractures, eight obtained a satisfactory outcome and the ninth case had an unsatisfactory outcome. In contrast, all seven children with troublesome fractures had an unsatisfactory outcome and the difference was highly significant (p = 0.0007). CONCLUSION: The authors strongly advise discussing the outcome of troublesome fractures with the parents and also advise documenting this in the file (prior to management) for medico-legal reasons.

Matched unrelated bone marrow transplantation for combined immunodeficiency.

Bone marrow transplantation (BMT) from siblings is the treatment of choice for severe combined immunodeficiency (SCID). The objective of this study was to evaluate the efficiency of BMT from matched unrelated donors (MUD) in congenital immunodeficiencies when a sibling donor is unavailable. Sixteen consecutive patients with SCID (n = 9) and CID (n= 7), were referred for an unrelated donor search. Acceptable donors were found for all patients. Fifteen patients received busulfan and cyclophosphamide pretransplant conditioning. One patient had an early loss of graft and was reconditioned using cyclophosphamide and total body irradiation. The graft-versus-host disease (GVHD) prophylaxis used was methylprednisolone, cyclosporin A with or without methotrexate. Neutrophil engraftment was rapid and was achieved in all patients within a mean of 15.4 days. Only 13 episodes of fever were recorded shortly after BMT. GVHD of grade II or more was apparent in 2/9 (22%) of SCID patients and in 4/7 (57%) of CID patients. Overall survival was 75% with a mean follow-up of 47.4 months (range 18-101). Six out of nine SCID patients (67%) and 6/7 (86%) of CID patients are alive and well. Eleven patients had normal humoral immunity, and cell-mediated immunity as measured by flow cytometry and mitogenic responses, was intact in all patients. Intradermal candida skin test was positive in 9/10 patients tested. We conclude that BMT from MUD results in rapid engraftment and is therefore associated with a low rate of infection contributing to the improved survival rate. The protocol used is especially favorable for patients with combined immunodeficiency.

The burden of uncomplicated cases of chickenpox in Israel.

OBJECTIVE: The aim of this study was to assess the direct medical burden and work loss associated with uncomplicated chickenpox in Israel. METHODS: A total of 155 otherwise healthy children and adolescents with chickenpox were recruited from 10 physician offices in central Israel. Direct and indirect medical burdens were determined by caregiver interview. RESULTS: Mean age was 3.3 +/- 2.3 years. 51% of the patients were under three years of age. Each patient made on average 1.15 visits to a general practitioner. Most patients were taken to the Doctor's office only once during the illness while 23 patients (15%) were seen twice. Three patients were referred to the emergency room. Antihistamines (39%) and Calamine lotion (28%) were the most frequently prescribed medications, followed by acyclovir (17%) and antibiotics (6%). Following the patient's illness there were 72 cases of secondary spread of varicella to household members. The individuals who cared for the child missed a combined total of 2.5 days from work (on average per varicella episode). CONCLUSIONS: Israeli children acquire chickenpox at a younger age than children in North America and England and consume more prescribed medications. While the work loss in the present study was comparable to previous reports, the direct medical costs inflicted by this infection in Israel are not negligible even for uncomplicated cases.

Allergy to sesame in humans is associated primarily with IgE antibody to a 14 kDa 2S albumin precursor.

The goal of this study was to identify and characterise the major allergen(s) of sesame seed. Detection of specific IgE to sesame proteins was performed with Pharmacia CAP System and Western blotting, after separation of sesame proteins by SDS-PAGE, using sera from 28 subjects diagnosed as allergic to sesame. The major allergen was separated by gel filtration chromatography and identified by selective proteolysis followed by peptide sequence analyses, employing electrospray-ionization mass spectrometer. Twenty-four of the 28 subjects had sesame-specific IgE. A 14 kDa protein belonging to the 2S albumin family was recognised by 22 of the 24 sera used. Subjecting the 14 kDa after HPLC separation to proteolysis with Lys C yielded 3 peptides, but only one reacted positively in the dot blot test. This peptide, corresponds in the whole protein chain to residues 24-94. The reactivity of the 14 kDa protein with most of the sera indicates that this is the major sesame allergen, later identified as 2S albumin precursor; and its peptide which reacted positively in the dot blot test evidently contains an epitope(s). Some minor sesame allergens, of higher molecular weight, were also revealed.

Evaluation of a possible inflammatory response after appendectomy for non-perforated appendicitis in children.

BACKGROUND: The inflammatory process in the post-appendectomy period is not well characterized. In a pilot study, we prospectively followed the kinetics of different inflammatory mediators before and after appendectomy in children, and compared the results of the groups open appendectomy (OA) and laparoscopic appendectomy (LA). MATERIAL AND METHODS: Levels of sP-selectin, tPA, MCP-1, IL-6, IL-8, sVCAM-1, and sCD40L were measured before appendectomy and on the next three consecutive days in the serum of 25 children (16 males and 9 females) aged 7 - 16 years (mean 12.6+/-2.47 years) with non-perforated acute appendicitis. RESULTS: LA and OA were performed in 16 and 9 patients respectively. None of the markers of inflammation differed significantly by surgical approach at any point of observation. However, sP-selectin, MCP-1 and sVCAM-1 levels were found to have significantly different postoperative kinetics with a trend towards higher values in the laparoscopic group compared to the open appendectomy group (p=0.034, p=0.016 and p=0.025, respectively). CONCLUSIONS: The cytokines sP-selectin, MCP-1 and sVCAM-1 may play a role in the possible post-appendectomy cytokine activation after non-perforated appendicitis. Since this phenomenon is more evident after LA than after OA, the contribution of the different LA procedures has to be further investigated.

PFAPA syndrome: new clinical aspects disclosed.

BACKGROUND: The recently described PFAPA (Periodic Fever, Aphthous stomatitis, Pharyngitis and Adenitis) syndrome is characterised by periodic fever, aphthous stomatitis, pharyngitis and adenitis. However, there are currently relatively few data on the natural history of this syndrome. OBJECTIVE: To describe the presentation, clinical course, doctors' awareness, therapeutic response and long-term follow-up of children with PFAPA syndrome. METHODS: Children with PFAPA syndrome referred over a 5-year period (from January 1999 to January 2004) were enrolled in the study. Data were gathered from medical records, parents' interviews, physical examination and telephone calls. RESULTS: 54 patients with PFAPA syndrome were evaluated. Our patients had a higher rate of abdominal pain (65%) and a lower rate of aphthous stomatitis (39%) than those in previous reports. Four different patterns of disease evolution were identified, including the relatively common (n = 14, 26%) and newly described course of alternating remissions and relapses. The remissions lasted 8.5 months on average (range 4-36 months). Diagnosis was established by primary paediatricians in 30 of 54 (56%) patients. However, a substantial delay in diagnosis was apparent (mean 15 months). Episodes were curtailed by a much lower dose of prednisone or equivalent corticosteroid (mean 0.6 mg/kg/day, range 0.15-1.5 mg/kg/day) than reported previously. Tonsillectomy was successful in the prevention of recurrence of further episodes in all six patients who underwent the procedure. CONCLUSIONS: We describe several new characteristics of PFAPA syndrome in children, contributing to our knowledge of this relatively unrecognised but troublesome syndrome. Early diagnosis and appropriate treatment can markedly improve the quality of life of both patients and families.

Celiac disease associated with familial chronic urticaria and thyroid autoimmunity in a child.

An 11-year-old girl presented with chronic urticaria (CU), antithyroid antibodies, and anemia. Celiac disease was diagnosed. The family history was positive for maternally derived CU and thyroid autoimmunity in three generations. Human leukocyte antigen typing disclosed human leukocyte antigen DQA1*0501 DQB1*0201 in both mother and child. CU was unresponsive to a gluten-free diet despite clinical and laboratory resolution of celiac disease in contrast to previous reports in adults. We believe that this is the first report of this association in a child, highlighting that CU may be a part of the spectrum of autoimmune phenomenon related to celiac disease.

Clinical utility of high-resolution pulmonary computed tomography in children with antibody deficiency disorders.

OBJECTIVE: To assess the value of high-resolution computed tomography (HRCT) in determining the extent and significance of lung disease in children with antibody deficiency states. MATERIALS AND METHODS: Seventy HRCT scans performed on 37 children with various antibody deficiency disorders over a 5-year period were retrospectively scored using a previously described demerit scoring system (0-25 with 0 = worst, 25 = best). Points are subtracted from 25 with increasing severity of disease. The potential correlations between CT scores and clinical factors, including age at diagnosis, age at CT, type of immunoglobulin deficiency, length of respiratory symptoms before diagnosis, number of pneumonias before diagnosis, type, length and success of therapy, patient compliance and pulmonary function tests (PFTs), were assessed. RESULTS: Of the 37 children, a demonstrated 22 abnormal scans (CT score < or = 22). All nine demonstrated bronchiectasis with a lower lobe and right middle lobe predominance. Statistically significant correlations were seen between severity of lung disease (CT score) and length of respiratory symptoms before diagnosis (p = 0.01), success of therapy (P = 0.001) and PFTs (P = 0.0008). Of seven children who were followed with repeated scans, 4 of the 7 demonstrated CT scores which improved on high-dose intravenous immunoglobulin replacement therapy. CONCLUSION: HRCT is a useful adjunct to demonstrate the extent and severity of lung disease at diagnosis and during therapy. Correlation with clinical factors suggests a higher risk group needing more aggressive management.

Two novel mutations in a purine nucleoside phosphorylase (PNP)-deficient patient.

Purine nucleoside phosphorylase (PNP) deficiency is a rare autosomal recessive disease, which presents clinically as severe combined immunodeficiency (SCID). We report here two novel mutations in the PNP gene that result in SCID phenotype, in a single patient. The maternal-derived allele carries a C to T transition in exon 2 resulting in a premature stop codon at amino acid 57. The paternal-derived mutation is a G to A transition at position +1 in intron 3, causing a complete skipping of exon 3 and a reading frameshift at the exon 2-exon 4 junction. The predicted polypeptide encoded by the aberrantly spliced mRNA terminates prematurely after only 89 amino acids. Both mutations predict severely truncated proteins resulting in a complete deficiency of PNP enzymatic activity, yet the development of profound immunodeficiency in this patient is greatly delayed.

An outbreak of echovirus 13 meningitis in central Israel.

Until recently, echovirus 13 has been a very rare cause of aseptic meningitis. We investigated an outbreak of echovirus 13 in central Israel during the summer of 2000 using a prospective case control study and a retrospective study. Echovirus 13 was isolated from 79 cerebrospinal fluid (CSF) specimens from different medical centres in central Israel. Patients' ages ranged from 10 days to 41 years (95% < 15 years, M/F ratio 62/38). A total of 128 patients with clinical aseptic meningitis were admitted to the Department of Pediatrics during the outbreak (aged 10 days to 18 years, mean 5.4 years), and 58 CSF samples were processed for viral cultures. Thirty of them did not grow any virus, 26 samples yielded echovirus 13, and 2 samples echovirus 7. The clinical features of patients with echovirus 13 in the CSF were similar to those in whom no virus was isolated or those infected with other enteroviral strains except for higher rate of fever on admission, and prolonged time with fever following the diagnosis in the echovirus 13 patients. CSF cell count varied from 4 to 2,333 cells/mm3 with polymorphonuclears (PMN) predominant in 90% of our patients. In a case-control study there was no significant difference between patients and matched controls with regard to parameters such as: day care attendance, recreation in summer camp, swimming pools and at the beach, and consumption of tap water. All the patients in our series recovered fully with no neurological abnormalities. The illness caused by echovirus 13 was benign and involved mainly patients younger than 15 year of age. Several features that characterized this outbreak include relatively high WBC in the blood and a minent CSF PMN response.

The outcome of patients with hypogammaglobulinemia in infancy and early childhood.

A 10-year prospective cohort study followed the evolution of antibodies in children less than 4 years of age with hypogammaglobulinemia. Three patterns were identified: in group 1, immunoglobulins and antibody production normalized;iin group 2, patients continued to have low IgG levels; and in group 3, IgG levels normalized but antibody levels were transient. Statistical analysis showed that invasive infection or low tetanus antibodies at presentation were associated with the development of significant humoral immunodeficiency.

Diuretic-natriuretic actions and pressor effects of big-endothelin (1-39) in phosphoramidon-treated rats.

The effects of phosphoramidon, a metalloproteinase inhibitor, on the pressor and renal actions of big-endothelin (BET), the precursor of porcine Endothelin-1 (ET), was studied in rats. In control rats, BET (0.3, 1.0, and 3.0 nmol/kg) elicited a marked increase in mean arterial blood pressure (from 110 +/- 7 to 105 +/- 7, 120 +/- 8, 147 +/- 6 mm Hg, respectively), and a prominent, dose-dependent, diuretic and natriuretic response (fractional sodium excretion (FENa) increased from 0.4 +/- 0.2 to 0.8 +/- 0.2, 3.1 +/- 0.1, and 8.5 +/- 1.7%, respectively). Pretreatment with phosphoramidon (10 mg/kg + 0.25 mg/kg/min) completely abolished the increase in blood pressure induced by BET, but the diuretic-natriuretic effects were only partially inhibited (FENa increased from 2.0 +/- 0.9 to 3.7 +/- 1.5, 3.9 +/- 1.3, and 4.3 +/- 1.2%, respectively, P < 0.05). Rats treated with phosphoramidon only had no natriuresis over time (FENa changed from 1.9 +/- 0.5 to 2.3 +/- 0.3, 1.6 +/- 0.4, 1.7 +/- 0.6 respectively, P--NS). The data suggest that, unlike the vascular type of the enzyme, the renal endothelin converting enzyme is relatively insensitive to phosphoramidon. Further, diuresis and natriuresis can be induced by BET in the absence of any pressor effect.

Cerebral vasculitis associated with chronic mucocutaneous candidiasis.

Chronic mucocutaneous candidiasis is a heterogenous group of disorders, associated with a variety of autoimmune disorders and a broad spectrum of immune aberrations. We describe 2 patients with chronic mucocutaneous candidiasis who had cerebrovascular disease with severe neurologic sequelae. Results of angiography of cerebral vessels and brain biopsy in one were consistent with the diagnosis of cerebral vasculitis.