Neuro-psychiatric symptoms in directly and indirectly blast exposed civilian survivors of urban missile attacks.

BACKGROUND: Blast-explosion may cause traumatic brain injury (TBI), leading to post-concussion syndrome (PCS). In studies on military personnel, PCS symptoms are highly similar to those occurring in post-traumatic stress disorder (PTSD), questioning the overlap between these syndromes. In the current study we assessed PCS and PTSD in civilians following exposure to rocket attacks. We hypothesized that PCS symptomatology and brain connectivity will be associated with the objective physical exposure, while PTSD symptomatology will be associated with the subjective mental experience. METHODS: Two hundred eighty nine residents of explosion sites have participated in the current study. Participants completed self-report of PCS and PTSD. The association between objective and subjective factors of blast and clinical outcomes was assessed using multivariate analysis. White-matter (WM) alterations and cognitive abilities were assessed in a sub-group of participants (n = 46) and non-exposed controls (n = 16). Non-parametric analysis was used to compare connectivity and cognition between the groups. RESULTS: Blast-exposed individuals reported higher PTSD and PCS symptomatology. Among exposed individuals, those who were directly exposed to blast, reported higher levels of subjective feeling of danger and presented WM hypoconnectivity. Cognitive abilities did not differ between groups. Several risk factors for the development of PCS and PTSD were identified. CONCLUSIONS: Civilians exposed to blast present higher PCS/PTSD symptomatology as well as WM hypoconnectivity. Although symptoms are sub-clinical, they might lead to the future development of a full-blown syndrome and should be considered carefully. The similarities between PCS and PTSD suggest that despite the different etiology, namely, the physical trauma in PCS and the emotional trauma in PTSD, these are not distinct syndromes, but rather represent a combined biopsychological disorder with a wide spectrum of behavioral, emotional, cognitive and neurological symptoms.

A case of mirtazapine-induced spontaneous orgasms in a female patient.

This is a case report of a 51-year-old woman admitted as a psychiatric outpatient with symptoms of moderate to severe depression and anxiety. She had received anti-depressants prior to her admission. The patient did not have a medical history of mania or hypomania, and did not complain of any sexual side-effects when taking prior medications. She was diagnosed in our clinic with mixed anxiety-depressive disorder. Due to lack of improvement she was commenced on mirtazapine and after three days complained of spontaneous orgasms and increased libido. The sexual symptoms resolved gradually after a few days and reappeared upon every dosage increase. On discontinuation of mirtazapine the side effects subsided. To the best of the author's knowledge this is the first report of spontaneous orgasms following treatment with mirtazapine.

Erythropoietin deficiency causes anemia in nephrotic children with normal kidney function.

Anemia in persistent nephrotic syndrome (NS) has been described in a few case reports but has not been studied systematically. We present a group of 19 children with NS who developed anemia before the deterioration of kidney function. The aim of our study is to determine whether erythropoietin (EPO) and/or iron deficiency are causative factors and to evaluate the effect of EPO replacement therapy. Serum EPO levels, iron status, and vitamin B(12) concentrations were measured in nephrotic patients with anemia (NS-A) and compared with those of nephrotic children with normal hemoglobin (Hb) levels (NS-NHb; n = 13). Two control groups consisted of age-matched patients without kidney disease or hypoxemia with either iron deficiency anemia (IDA; n = 19) or normal Hb concentrations (NHb; n = 16). Most NS-A patients experienced persistent steroid-resistant NS, whereas most NS-NHb children had steroid-responsive NS. Although serum iron, ferritin, and B(12) levels were significantly lower in NS-A children, appropriate replacement therapy that resulted in normalization of ferritin and/or cobalamin levels did not lead to correction of the anemia. NS-A patients had greater EPO levels than those without anemia (21.6 +/- 3.3 versus 5.5 +/- 0.8 IU/L; P: < 0.001), but their response to anemia was inappropriately low compared with IDA children (EPO, 94.6 +/- 15.1 IU/L) despite similar Hb concentrations. EPO therapy for 4 to 9 months in 6 NS-A children with Hb levels less than 9 g/dL led to resolution of the anemia. In conclusion, anemia is a common feature of persistent NS that develops before the deterioration of kidney function. Depletion of iron stores may contribute to the development of anemia, but iron replacement therapy is ineffective. Nephrotic patients have EPO deficiency with a blunted response to anemia. The EPO deficiency is amenable to EPO therapy, which is recommended for this group of patients.

Infantile variant of Bartter syndrome and sensorineural deafness: a new autosomal recessive disorder.

The infantile variant of Bartter syndrome (IBS) is usually associated with maternal polyhydramnios, premature birth, postnatal polyuria and hypokalemic hypochloremic metabolic alkalosis and a typical appearance. IBS is thought to be an autosomal recessive trait. Several congenital tubular defects are associated with sensorineural deafness (SND). However, an association between the IBS and SND has not been reported so far. Here we describe 5 children of an extended consanguineous Bedouin family with IBS and SND. In 3 of the cases, the typical electrolyte imbalance and facial appearance were detected neonatally. SND was detected as early as age 1 month, suggesting either coincidental homozygotization of 2 recessive genes or a pleiotropic effect of one autosomal recessive gene. This association suggests that evaluation of SND is warranted in every case of IBS.

Possible oxidative stress involvement in congenital dyserythropoietic anemia type 1.

INTRODUCTION: Congenital dyserythropoietic anemia type 1 (CDA1) patients may suffer from iron overload, associated with oxidative damage. The aim of this study was to evaluate possible involvement of oxidative stress in the pathogenesis of CDA1. STUDY DESIGN: : Blood samples from 10 children diagnosed as CDA1 patients from five Bedouin families, were studied. In this study, activities of superoxide dismutase and catalase were evaluated as well as methemoglobin, plasma total thiols, plasma total antioxidant capacity and glycerol lysis time. RESULTS: Normal values were found for superoxide dismutase, methemoglobin, trolox equivalent antioxidant capacity and total plasma thiols in CDA1 patients. However average catalase levels were significantly reduced (P<0.001) and glycerol lysis test was significantly prolonged (P<0.001). Ferritin levels, which were slightly increased in all patients, positively correlated with catalase values (r = 0.74, P = 0.022). CONCLUSION: Oxidative stress has not been proven in CDA1 pediatric patients. Some indications of oxidative damage exist, but it may not be directly related to the mechanism of anemia.

Acute pancreatitis in children following envenomation by the yellow scorpion Leiurus quinquestriatus.

Plasma immunoreactive cationic trypsin (ICT), which is a specific and highly sensitive indicator of pancreatic injury, was measured in 14 children with signs of systemic envenomation following a sting by the scorpion Leiurus quinquestriatus. High ICT levels were found in 13 children (93%), indicating that acute pancreatitis is a common complication of envenomation by this scorpion. The pancreatitis may account for the abdominal pain and vomiting commonly seen in scorpion envenomation and may also contribute to the agitation and discomfort noted in young children.

[Henbane (Hyoscyamus reticulatus) poisoning in children in the Negev].

During 1984-1989, 19 Bedouin children, 4-8 years old, were hospitalized because of henbane plant (Hyoscyamus reticulatus) poisoning. There were 14 cases in the autumn, 3 in the spring and 2 in the summer. The most prominent signs were altered state of consciousness (including deep coma in 3) and flushed dry, warm skin in all. Pupils were dilated in 18 of the 19 and restlessness and hallucinations were present in 17. Less common were vomiting, increased tendon reflexes, convulsions, involuntary movements, ataxia, hypertension, hyperpyrexia and tachycardia. Therapy included intravenous physostigmine in 7 and sedatives (diazepam and triclofos) in 6. All were free of symptoms within 24 hours of admission. Henbane may grow as an annual or biennial. Renewed growth of leaf rosettes occurs before the first rains and they attract attention in the fields. The parts of the plant eaten by most of the children were the roots, which are easily mistaken for the edible roots of other plants. The main alkaloids in henbane are atropine (hyoscyamine) and scopolamine (hyoscine) which explains the clinical picture of mixed stimulation and depression of the brain. Educational measures should be undertaken to prevent poisoning of Bedouin children by eating such plants.

[Evans syndrome in a child].

A Bedouin girl, aged 2 3/12, was first seen at the age of 9 months for sequential onset of Coombs-positive hemolytic anemia and immune thrombocytopenia. Comprehensive laboratory workup revealed no underlying disease. Evans' syndrome, relatively rare in childhood, was diagnosed and corticosteroid therapy initiated. She responded well and normal hemoglobin and thrombocyte counts were achieved within a month. All attempts at tapering-off the dose of corticosteroids resulted in relapses, until high-dose intravenous gamma-globulin was given.

[Hypocalcemia associated with heart failure in infants].

A 2.5-month-old girl and a 34-day-old boy with clinical and X-ray signs of heart failure, and hypocalcemia as well, are presented. Cardiologic investigation revealed no organic causes and in both cases the signs of heart failure resolved only when calcium levels were restored to normal.

Post-traumatic anxiety associates with failure of the innate immune receptor TLR9 to evade the pro-inflammatory NFκB pathway.

Post-traumatic anxiety notably involves inflammation, but its causes and functional significance are yet unclear. Here, we report that failure of the innate immune system Toll-like receptor 9 (TLR9) to limit inflammation is causally involved with anxiety-associated inflammation and that peripheral administration of specific oligonucleotide activators of TLR9 may prevent post-traumatic consequences in stressed mice. Suggesting involvement of NFκB-mediated enhancement of inflammatory reactions in the post-traumatic phenotype, we found association of serum interleukin-1ß increases with symptoms severity and volumetric brain changes in post-traumatic stress disorder patients. In predator scent-stressed mice, the moderate NFκB-activating oligonucleotides mEN101 and its human ortholog BL-7040, but not the canonic NFκB activator oligonucleotide ODN1826, induced anxiolytic effects. In stressed mice, peripherally administered mEN101 prevented delayed stress-inducible serum interleukin-1ß increases while limiting stress-characteristic hippocampal transcript modifications and the anxiety-induced EGR1-mediated neuronal activation. Attesting to the TLR9 specificity of this response, BL-7040 suppressed NFκB-mediated luciferase in transfected cells co-expressing TLR9, but not other TLRs. Furthermore, TLR9-/- mice were mEN101 and BL-7040 resistant and presented unprovoked anxiety-like behavior and anxiety-characteristic hippocampal transcripts. Our findings demonstrate functional relevance of TLR9 in protecting stressed mammals from overreacting to traumatic experiences and suggest using oligonucleotide-mediated peripheral TLR9 activation to potentiate the innate immune system and prevent post-traumatic inflammation and anxiety.

Nephrocalcinosis in pseudohypoaldosteronism and the effect of indomethacin therapy.

We report four patients with pseudohypoaldosteronism, aged 5 months to 5 years. All patients had hypercalciuria and three had nephrocalcinosis. Two patients with nephrocalcinosis were treated with indomethacin. Polydipsia decreased and appetite and weight gain improved within 14 days of therapy. Hypercalciuria, polyuria, and creatinine clearance decreased 30% to 50% and urinary prostaglandin E2 levels decreased fourfold to eightfold.

Pediatric urolithiasis in southern Israel: the role of uricosuria.

We describe three cases of severe obstructive uropathy in children under 2 years of age, due to radiolucent renal stones. Metabolic work-up revealed only normouricemic hyperuricosuria (HU) as the single identifiable risk factor for urolithiasis (UL) in these infants. We reviewed records of 66 cases of pediatric UL seen in our service over an 8-year period. UL prevalence was greater for Bedouin than for Jewish children (1.02 vs. 0.13 cases/1,000 inhabitants at risk respectively, P<0.01). HU (>0.6 mg uric acid/dl GFR) was the only biochemical risk factor that differed between Bedouin and Jewish children (mean uric acid excretion index 0.8+/-0.39 vs. 0.55+/-0.26 mg/dl GFR respectively, P<0.05). Bedouin children comprised 85% of patients in the HU group versus 59% in the non-hyperuricosuric group (P<0.05). The mean age of onset of UL was 38+/-44 months and 93+/-52 months in the HU and the non-HU group, respectively (P<0.05). The UA excretion index in the HU group was inversely correlated with age (r=0.41, P<0.01) and its slope and constant were different from an age-matched non-UL control population. In conclusion, pediatric UL in southern Israel is predominant in Bedouin toddlers. HU was the only identifiable biochemical risk factor that could explain this difference.

Prenatal diagnosis of Bartter syndrome.

Bartter syndrome, an autosomal recessive disorder of hyperaldosteronism and increased plasma renin, was suspected in an at-risk pregnancy due to the early occurrence of polyhydramnios. Further establishment of the diagnosis was accomplished by demonstrating increased levels of aldosterone in amniotic fluid and fetal cord blood. Electrolyte levels did not differ significantly from reported controls. It is thus suggested that polyhydramnios is the result of increased fetal urine output in Bartter syndrome and that amniotic fluid aldosterone is a reliable marker for the prenatal diagnosis of this condition.

Anti-D exerts a very early response in childhood acute idiopathic thrombocytopenic purpura.

Acute idiopathic (immune) thrombocytopenic purpura (ITP) in the pediatric population is a disease in which autoimmune features are mainly self-limited, with a reported mortality of 0.1-0.5%. Major treatment requires intravenous gammaglobulins (i.v. IgG) and corticosteroids. Recently a new globulin, anti-D, has been introduced. The authors have treated 25 children suffering from acute idiopathic thrombocytopenic purpura, with an i.v. anti-D dose of 75 microg/kg as the first treatment. Eligibility criteria included a platelet count < 15,000 and Rh+. Post-treatment response was 76% > 20,000 platelets at 6-10 h and 80% > 50,000 platelets at 48 h; three patients developed chronic idiopathic thrombocytopenic purpura. There were 5/25 patients who did not respond to the initial dose and received i.v. IgG and corticosteroids, 2/5 with a positive response (platelets > 20,000). Side effects consisted of chills (9/25), fever > 38 degrees C (6/25), headache and vomiting (1/25), hemolysis (20/25) from 0.9-6.9 g%, and decrease in hemoglobin levels. One patient needed a blood transfusion after his Hbg decreased from 12.4 to 5.5 g%. The results indicate that anti-D is an effective treatment in acute ITP, but with side effects. Administration of steroids and antipyretics prior to anti-D treatment may prevent the side effects.

Protein C and protein S in pediatric nephrotic patients.

Nephrotic syndrome (NS) is associated with an increased incidence of various thromboembolic complications in adult patients. It was found to be due to elevated factor IX (FIX) F.VII, F.VIII, F.V, fibrinogen, thrombocytosis and increased platelet reactivity. Acquired AT-III deficiency, reduced functional levels of protein S and reduced activity of protein C were also reported. We evaluated 15 children aged 1 to 13 years. Thirteen of these children suffered from nephrotic syndrome and two others had non-nephrotic proteinuria. All patients but one were normotensive. Two patients were not steroid responsive. Serum creatinine was normal for age in 14 patients. Kidney biopsy was carried out only in three children. Haemostatic parameters included protein C and S antigenicity in plasma and urine. Plasma levels of protein C and protein S were within the normal range. Protein C antigenicity in urine was increased in five children out of 14 examined. Protein S in urine was increased in seven out of 12 children examined. No thromboembolic phenomena were documented even though protein C and protein S antigenicity were identified in the urine.

Neonatal manifestations of congenital dyserythropoietic anemia type I.

Congenital dyserythropoietic anemia type I is a rare inherited bone marrow disorder characterised by macrocytic anemia with pathognomonic morphological ultrastructural features in erythroid precursors. The disease is usually not diagnosed in the neonatal period. In a retrospective study of 31 patients we found that 17 were first seen in the neonatal age with significant anemia (birth hematocrit 0.34 +/- 0.07); 14 of the 17 infants also had early jaundice. Six infants were small for gestational age and two had syndactyly. Although rare, congenital dyserythropoietic anemia type I should be considered in the differential diagnosis of neonatal anemia.

Oligohydramnion, renal failure and no pulmonary hypoplasia in glomerulocystic kidney disease.

Two newborns with glomerulocystic kidney disease manifesting as late onset oligohydramnion and neonatal anuria, yet without severe respiratory distress, are presented. They had a similar perinatal course and associated clinical manifestations. No associated congenital or inherited malformation syndrome could be defined. Both infants' parents were first degree cousins and belonged to the same small Bedouin tribe, and neither they nor the infants' siblings had polycystic kidneys or renal insufficiency, pointing to either a possible genetic etiology or a common external toxic exposure.