Gerstmann tetrad in Leopard syndrome

We report a 12-year-old boy with multiple lentigines (Leopard) syndrome who was evaluated for learning difficulties and Gerstmann tetrad syndrome (i.e., dyscalculia, left-right disorientation, finger agnosia, and dysgraphia). Cranial computed tomography revealed left ventriculomegaly, more pronounced in the occipital horn suggesting mild atrophy of the left parietal lobe. This is the first report of an association between the Leopard and Gerstmann syndromes and one of the few to demonstrate a computed tomographic abnormality in the latter.     

Tolerance to morphine effects on renal disposition of xenobiotics in mice

Morphine administration (20 mg/kg s.c.) slowed renal elimination of phenol red in mice, raising plasma levels of this dye and reducing its levels in urine. After 9 days of twice daily morphine injections up to 100 mg/kg, an acute 20 mg/kg morphine challenge did not produce analgesia or hypothermia as in naive mice. This multiple dose morphine regimen also induced tolerance to the effects of the narcotic on plasma and urine levels of phenol red. Morphine, 20 mg/kg, reduced plasma p-aminohippurate clearance by 72% in naive mice but only by 56% in tolerant mice. However, reduction of iothalamate clearance after an acute morphine challenge did not show a statistically significant difference between naive and tolerant mice. These findings suggest that tolerance is more readily induced to the effects of narcotic on renal blood flow and/or tubular function than to reduction of glomerular filtration. Tolerance to the acute effects of morphine on phenol red disposition is probably due to lessened response of blood flow or tubular function in chronically dosed mice.     

Autoantibodies to neuroblastoma cell surface antigens in neuropsychiatric lupus

A human neuroblastoma cell line, LA-N-1 was used as a target cell in a I131 radiolabeled staphylococcal protein-A (I131-SpA) binding assay, to characterize the pattern of antineuronal activity of human sera in fifty-four cases of systemic lupus erythematosus (SLE) including twenty-six patients with neuropsychiatric manifestations of SLE (LE-CNS), out of which ten were pediatric patients aged eleven to eighteen years, thirty-six normal donors and sixteen rheumatoid arthritis patients. The IgG binding activity of normal control sera with LA-N-1 neuroblastoma cells was determined to be 998 +/- 490 cpm I131-SpA, per 5 micrograms LA-N-1 protein (mean +/- SD), 2936 +/- 2607 cpm I131-SpA per 5 micrograms LA-N-1 protein for rheumatoid arthritis patients, 5109 +/- 3304 cpm I131-SpA per 5 micrograms LA-N-1 protein for SLE patients. The binding activity of for LE-CNS patients sera was: 10 565 +/- 2993 and 15 346 +/- 2993 cpm I131-SpA per 5 micrograms LA-N-1 protein, for the pediatric and adult group of patients respectively. Absorption assays disclosed that the antineuronal IgG autoantibody detected in the LE-CNS group of patients is cross reacting with human adult brain, while the anti-neuronal activity of rheumatoid arthritis and SLE patients could be removed by sequential absorption with homogenates of human lung, liver, and kidney, fetal calf serum, human muscle and human lymphocytes. We conclude that detection of autoantibodies binding to LA-N-1 human neuroblastoma cells may be helpful in the diagnostic workup of pediatric and adult LE-CNS patients.     

A corticosteroid-induced gene expressing an "IsK-like" K+ channel activity in Xenopus oocytes.

Screening a rat colon cDNA library for aldosterone-induced genes resulted in the molecular cloning of a cDNA whose corresponding mRNA is strongly induced in the colon by dexamethasone, aldosterone, and a low NaCl diet. A similar mRNA was detected in kidney papilla but not in brain, heart, or skeletal muscle. Xenopus laevis oocytes injected with cRNA synthesized from this clone, designated CHIF (channel-inducing factor), express a K(+)-specific channel activity. The biophysical, pharmacological, and regulatory characteristics of this channel are very similar to those reported before for IsK (minK). These include: slow (tau > 20 s) activation by membrane depolarization with a threshold potential above -50 mV, blockade by clofilium, inhibition by phorbol ester, and activation by 8-bromoadenosine 3',5'-cyclic monophosphate and high cytoplasmic Ca2+. The primary structure of this clone, however, shows no homology to IsK. Instead, CHIF exhibits > 50% similarity to two other short bitopic membrane proteins, phospholemman and the gamma subunit of Na+K(+)-ATPase. The data are consistent with the possibility that CHIF is a member of a family of transmembrane regulators capable of activating endogenous oocyte transport proteins.     

Cryptococcal meningitis in a child with hyperimmunoglobulin E syndrome

A 13-year-old boy with hyperimmunoglobulin E (hyper-IgE) syndrome presented with headache, blurred vision, photophtobia and bilateral papilledema due to cryptococcal meningitis. Treatment with amphotericin B, and S-fluorocytosine for several weeks and repeated lumbar punctures did not reduce the intracranial pressure, and a myeloperitoneal shunt was performed. The child was maintained on fluconazole for an additional six months. Patients with hyper-IgE syndrome are at increased risk of opportunistic fungal infections such as cryptococcal meningitis.     

Prolonged croup due to herpes simplex virus infection

Herpes simplex virus (HSV) is an uncommon cause of acute laryngitis in immunocompetent patients since it mostly occurs in immunocompromised subjects. We present two previously healthy children with prolonged gingivostomatitis and stridor (lasting 3 and 4 weeks) in whom HSV-1 was isolated from subglottal ulcers. Conclusion HSV should be considered a possible pathogen in cases of prolonged or atypical croup not only in immunocompromised or elderly patients but also in otherwise healthy children. Received: 10 March 1997 / Accepted: 20 September 1997     

Chronic granulomatous disease: Clinical,functional, molecular,and genetic studies. The Israeli experience with 84 patients

Chronic granulomatous disease (CGD) is an innate immunodeficiency with a genetic defect of the nicotinamide adenosine dinucleotide phosphate, reduced, oxidase components. This leads to decreased reactive oxygen species (ROS) production, which renders patients susceptible to life‐threatening infections. Over the course of 30 years, we diagnosed CGD in 84 patients from 61 families using functional, molecular, and genetic studies. The incidence of CGD in Israel is 1.05 per 100,000 live‐births in the Jewish population and 1.49 in the Israeli Arab population. We diagnosed 52 patients (62%) with autosomal recessive inheritance (AR‐CGD) and 32 (38%) with X‐linked recessive inheritance (XLR‐CGD). Consanguinity was detected in 64% of AR‐CGD families (14% in Jews and 50% in Israeli Arabs). We found 36 different mutations (23 in XLR‐CGD and 13 in AR‐CGD patients), 15 of which were new. The clinical spectrum of CGD varied from mild to severe disease in both XLR and AR forms, although the AR subtype is generally milder. Further, residual ROS production correlated with milder clinical expression, better prognosis and improved overall survival. Patients with recurrent pyogenic infections developed fibrosis and hyperinflammatory states with granuloma formation. The management of CGD has progressed substantially in recent years, evolving from a fatal disease of early childhood to one of long‐term survival. Our present cohort displays an encouraging 81% overall long term survival. Early hematopoietic stem cell transplantation is advisable before tissue damage is irreversible. Successful transplantation was performed in 18/21 patients. Therapeutic gene modification could become an alternative cure for CGD. Am. J. Hematol. 92:28–36, 2017. © 2016 Wiley Periodicals, Inc.     

Helicobacter pylori infection in patients with selective immunoglobulin E deficiency

AIM: To investigate the prevalence and clinical characteristics of Helicobacter pylori(H.pylori)-infected dyspeptic patients with selective immunoglobulin E deficiency(IgE d).METHODS: All individuals who underwent serum totalimmunoglobulin E(Ig E) measurement at the Leumit Healthcare Services(Israel) in 2012 were identified in an electronic database search(n = 18487).From these,selected case group subjects were ≥ 12 years of age and had serum total Ig E 2 k IU/L(n = 158).The control group was selected from a random sampling of the remaining subjects ≥ 12 years of age to obtain a case-control ratio of 1:20(n = 3160).Dyspeptic diseases,diagnosed no more than 5 years before serum total Ig E testing,were identified and retrieved from the electronic database using specific International Classification of Diseases diagnostic codes.Results of C13-urea breath tests were used to identify subjects infected with H.pylori.Categorical variables between case and control subjects were analyzed using Fisher's exact tests,whereas continuous variables were analyzed using χ2 tests.RESULTS: Dyspepsia was present in 27.2%(43/158) of case subjects and 22.7%(718/3160) of controls.Of these,significantly more case subjects(32/43,74.4%) than controls(223/718,31.1%) were positive for H.pylori(P 0.01).Esophagogastroduodenoscopy was performed in 19 case and 94 control subjects,revealing that gastritis was more prevalent in IgE d case subjects than in controls(57.9% vs 29.8%,P 0.05).Furthermore,a significantly greater proportion of case subjects presented with peptic duodenal ulcers(63.2% vs 15.9%,P 0.01).Histopathologic examination showed marked chronic inflammation,lymphoid follicle formation and prominent germinal centers,with polymorphonuclear cell infiltration of gastric glands,that was similar in case and control biopsy tissues.Finally,Ig Ed case subjects that underwent esophagogastroduodenoscopy were more likely to exhibit treatment-refractory H.pylori infections that require second-line triple antibiotic therapy(47.4% vs 11.7%,P 0.01).CONCLUSION: IgE d is associated with higher rates ofH.pylori-associated gastritis and peptic duodenal ulcers.