Haggit Hurvitz

Treatment with hypertonic saline versus normal saline nasal wash of pediatric chronic sinusitis

BACKGROUND Chronic sinusitis (CS) is a common disease in children, especially those with allergies, that is caused by impaired drainage from the sinuses. Hypertonic NaCl solution has been shown to increase mucociliary clearance and ciliary beat frequency. OBJECTIVE We performed a randomized double blind study to compare the effect of nasal wash with hypertonic saline (HS) (3.5%) versus normal saline (NS) (0.9%) on CS. METHODS Thirty patients with CS aged 3 to 16 years were studied. They were randomly divided into two treatment groups matched by age and severity of the disease. Each individual was treated with either HS or NS for 4 weeks. All patients were evaluated by two clinical scores (cough and nasal secretions/postnasal drip [PND]) and by a radiology score at the beginning of the study and after 4 weeks. RESULTS The HS group improved significantly in all scores (average +/- SD): cough score, from 3.6 +/- 0.51 to 1.6 +/- 0.74; nasal secretion/PND score, from 2.86 +/- 0.35 to 1.6 +/- 0.74; and radiology score, from 8.06 +/- 1.28 to 2.66 +/- 1.04. The NS treatment group showed significant improvement only in the PND score (from 2.66 +/- 0.49 to 1.53 +/- 0.83) but no significant change in both the cough score (from 3.53 +/- 0.52 to 3.33 +/- 0.49) and the radiology score (from 8.13 +/- 1.25 to 7.86 +/- 0.91). Clinical observation 1 month after the end of the study showed no change compared with the end of the study in both groups. CONCLUSION HS nasal wash is an efficient treatment of CS.

Evidence that Griscelli syndrome with neurological involvement is caused by mutations in RAB27A, not MYO5A

Griscelli syndrome (GS), a rare autosomal recessive disorder, is characterized by partial albinism, along with immunologic abnormalities or severe neurological impairment or both. Mutations in one of two different genes on chromosome 15q can cause the different subtypes of GS. Most patients with GS display the hemophagocytic syndrome and have mutations in RAB27A, which codes for a small GTPase. Two patients with neurological involvement have mutations in MYO5A, which codes for an actin-based molecular motor. The RAB27A and MYO5A gene products interact with each other and function in vesicle trafficking. We report the molecular basis of GS in a Muslim Arab kindred whose members have extremely variable neurological involvement, along with the hemophagocytic syndrome and immunologic abnormalities. The patients have normal MYO5A genes but exhibit a homozygous 67.5-kb deletion that eliminates RAB27A mRNA and immunocytofluorescence-detectable protein. We also describe the molecular organization of RAB27A and a multiplex polymerase chain reaction assay for the founder deletion in this kindred. Finally, we propose that all patients with GS have RAB27A mutations and immunologic abnormalities that sometimes result in secondary neurological involvement. The two patients described elsewhere who have MYO5A mutations and neurological complications but no immunologic defects may not have GS but instead may have Elejalde syndrome, a condition characterized by mild hypopigmentation and severe, primary neurological abnormalities.

Bloody diarrhea--a possible complication of sulfasalazine transferred through human breast milk.

Sulfasalazine very rarely causes bloody diarrhea. A 3-month-old infant had bloody diarrhea that could be related to sulfasalazine that had been taken by his mother and was transferred through his mothers breast milk. The patient was exclusively breast fed, and no other known etiological factors could be detected for the infants bloody diarrhea.

Recurrent acute disseminated encephalomyelitis associated with acute cytomegalovirus and Epstein-Barr virus infection.

We describe a 56 /12-year-old girl with recurrent episodes of acute disseminated encephalomyelitis following an acute cytomegalovirus infection and associated reactivated Epstein-Barr virus. Complete clinical recovery was obtained with intravenous immunoglobulin. (J Child Neurol 2000;15:421-424).

Acute Otitis Media in the first two months of life: characteristics and diagnostic difficulties.

Objective: To assess the clinical and laboratory features of acute otitis media (AOM) in infants younger than 2 months, to look for factors predicting bacterial otitis, and to evaluate the accuracy of AOM diagnosis among paediatricians. Methods: The study population comprised a cohort of 277 hospitalised infants up to 61 days old that were treated for the first episode of AOM in a paediatric department. We reviewed their medical records and analysed the demographic, clinical and laboratory data, and the diagnosis made by both paediatricians and otolaryngologists. Results: Presenting symptoms were mainly respiratory (70.0%) and fever (62.5%). The most common pathogens were Streptococcus pneumoniae and Haemophilus influenzae. Gram-negative bacilli grew in 10.5% of the infants. Multivariate analysis revealed that AOM in the second month of life was associated with male gender, concurrent bronchiolitis and diarrhea. Although high leukocyte count was associated with bacterial pathogen, more than 70% of the patients with positive culture had normal white blood cell counts. The paediatrician diagnosed only 45% of the patients subsequently diagnosed with AOM by an otolaryngologist. Conclusions: The absence of predictors for bacterial infection in more than 70% of bacterial AOM suggests that empirical antibiotic treatment should be advised for the young infants with AOM even when afebrile and with normal laboratory profile. A low diagnostic rate of AOM by the paediatrician emphasizes the need for improvement in examination skills and instrumentation to allow a thorough ear evaluation in children of a very young age.

The clinical course of bronchiolitis associated with acute otitis media

BACKGROUND Acute otitis media (AOM) is the most common bacterial co-infection of viral bronchiolitis. AIMS To evaluate the influence of AOM on the clinical course of bronchiolitis. SUBJECTS 150 children younger than 24 months old, diagnosed with bronchiolitis, hospitalised between December 1997 and May 1999. METHODS Body temperature, respiratory rate, oxygen saturation, and the need for oxygen supplementation were recorded on admission and daily throughout hospitalisation. Complete blood count, erythrocyte sedimentation rate, and assay for respiratory syncytial virus were performed on admission. All children were examined daily for the appearance of AOM. The clinical course of children with bronchiolitis and AOM was compared to those without AOM. RESULTS AOM was diagnosed in 79/150 (53%) children with bronchiolitis. Most were diagnosed within the first two days of hospitalisation. No significant difference was found in the clinical and laboratory findings on admission and on daily follow up between children with and without AOM. CONCLUSIONS This 2.5 year prospective study showed no difference in the course of bronchiolitis, whether an ear infection was present or not.

Prolidase deficiency: it looks like systemic lupus erythematosus but it is not

Three siblings with recalcitrant leg ulceration, splenomegaly, photosensitive rash, and autoantibodies were suspected of having prolidase deficiency. Urine was checked for iminodipeptiduria, fibroblasts were cultured and analyzed for prolidase activity, and DNA was extracted for identifying the causative mutation. Glycyl proline was found as the dominant dipeptide in the urine. The activity of proline dipeptidase in fibroblasts was 2.5% of control fibroblasts. Sequence analysis of the PEPD gene revealed a homozygous nonsense C→G transition at nucleotide 768. In conclusion, prolidase deficiency was diagnosed in siblings with skin ulceration autoantibodies and a lupus-like disease. A novel nonsense mutation was found, associated with the severe outcome of our patients.

Kingella kingae endocarditis and sepsis in an infant

Kingella kingae is a normal inhabitant of the upper respiratory tract which is being increasingly recognised as a pathogen in humans and usually causes septic arthritis and osteomyelitis [1, 5]. We describe a previously healthy infant who presented with fulminant sepsis and was found to have K. kingae endocarditis. A 10-month-old previously healthy male infant presented with a 12 h history of high fever, pallor, cough and severe dyspnoea following a few short episodes of fever during the previous 2 weeks. His parents reported that 2 months earlier he had an infected diaper rash with small abscess formation. His immunizations were up to date. There were no known previous cardiac problems or recurrent infections in either the child or his family. On admission he looked extremely sick, pale, dyspnoeic and lethargic with poor peripheral perfusion. Temperature was 40 C, heart rate 160/min, blood pressure 80/ 35 mm Hg, oxygen saturation 88% in room air. Bilateral fine crackles were heard over the lungs. Heart sounds were normal, with a 1/6 systolic murmur at the apex. There was prominent hepatosplenomegaly. No skin lesions or abnormal musculoskeletal findings were found. Laboratory tests showed the following: haemoglobin 5.5 g/dl, WBC 34·10/dl, platelets 50·10/dl and raised C-reactive protein (250 mg/l). He had impaired clotting with increased INR and activated partial thromboplastin time. Fibrinogen was low. Renal and liver functions were normal. A chest X-ray film revealed a moderately enlarged heart with mild congestion and small pleural effusions. Combined treatment with oxygen, intravenous cefuroxime, vancomycin, packed cells

Eicosanoids content in small intestinal mucosa of children with celiac disease.

Celiac disease (CD) is characterized by diarrhea, growth retardation, and weight loss in genetically susceptible subjects on a gluten-containing diet. The exact pathogenesis of CD is still obscure, but it is considered to be immunologically mediated. We have previously shown elevated prostaglandin E2 (PGE2) and thromboxane B2 (TxB2) content in small intestinal mucosa obtained from active celiac children. In the present study, we found significantly elevated PGE2, leukotriene B4 (LTB4), and leukotrienes C4,D4, and E4 (LTC4D4E4) content in small bowel mucosa from children suffering from CD on a gluten-containing diet in comparison to control subjects. PGE2 was 25,278 ± 7,761 vs. 4,478 ± 426 pg/mg of protein (mean ± SEM), respectively. LTB4 was 8,807 ± 3,706 vs. 403 ± 63 pg/mg of protein (mean ± SEM), respectively. LTC4D4E4 was 15,369 ± 4,085 vs. 2,998 ± 279 pg/mg of protein (mean ± SEM), respectively. We conclude that the elevated content of arachidonic acid metabolic products via cyclooxygenase and lipoxygenase pathways may contribute to the diarrhea and may be involved in the pathogenesis of mucosal injury.

Cellular and clinical report of new Griscelli syndrome type III cases.

The RAB27A/Melanophilin/Myosin‐5a tripartite protein complex is required for capturing mature melanosomes in the peripheral actin network of melanocytes for subsequent transfer to keratinocytes. Mutations in any one member of this tripartite complex cause three forms of Griscelli syndrome (GS), each with distinct clinical features but with a similar cellular phenotype. To date, only one case of GS type III (GSIII), caused by mutations in the Melanophilin (MLPH) gene, has been reported. Here, we report seven new cases of GSIII in three distinct Arab pedigrees. All affected individuals carried a homozygous missense mutation (c.102C>T; p.R35W), located in the conserved Slp homology domain of MLPH, and had hypomelanosis of the skin and hair. We report the first cellular studies on GSIII melanocytes, which demonstrated that MLPH(R35W) causes perinuclear aggregation of melanosomes in melanocytes, typical for GS. Additionally, co‐immunoprecipitation assays showed that MLPH(R35W) lost its interaction with RAB27A, indicating pathogenicity of the R35W mutation.