WFS1 mutations in Spanish patients with diabetes mellitus and deafness

Wolfram syndrome (WS) is an autosomal recessive neurodegenerative disorder characterised by early onset diabetes mellitus and progressive optic atrophy, as well as other clinical features such as deafness, diabetes insipida, renal tract abnormalities and diverse psychiatric illnesses. A gene responsible for WS was identified in 4p16.1 (WFS1). It encodes a putative 890 amino acid transmembrane protein expressed in a wide spectrum of tissues. Recently, a new locus for WS has been located on 4q22-24, providing additional evidence for the genetic heterogeneity of this syndrome. We have studied the presence of WFS1 variants in three groups of individuals: patients with diabetes mellitus, patients with deafness and patients with both conditions. A fourth group of healthy subjects was used as control. We have identified a total of 18 nucleotide changes in the WFS1 gene: three mutations and 15 polymorphisms. Six of these changes were previously undescribed. Four of the 15 polymorphisms studied among the patients group present statistical differences in the allelic and genotypic distribution when comparing affected vs control groups.     

Acute respiratory infection by human metapneumovirus in children in southern Brazil.

BACKGROUND: Human metapneumovirus (hMPV) has been described as an etiologic agent of acute respiratory infections (ARI), mainly in pediatric patients. Viral isolation is difficult and has low sensitivity, and consequently RT-PCR assays are currently used for detection. OBJECTIVES: Detect hMPV in ARI in hospitalized children in Southern Brazil; standardize a RT-PCR for routine hMPV diagnosis; validate a positive control for molecular tests; and perform phylogenetics analyses. STUDY DESIGN: Nasopharyngeal aspirates (NPA) from 156 hospitalized children were studied. A conserved region of the nucleoprotein gene was cloned, characterized and used to standardize an RT-PCR assay. Phylogenetic analyses were performed. Clinical data were obtained from medical records. RESULTS: hMPV was detected in 6.4% of the samples. Dyspnea and wheezing were frequently reported symptoms and the most common diagnoses were bronchiolitis, acute respiratory insufficiency or laryngotracheobronchitis. Nucleotide sequence alignment revealed 97.7% identity with genotype A1 of hMPV. The detection limit of hMPV genomes by RT-PCR in clinical samples was 180 copies/microL. CONCLUSION: This is the first report of the detection and genetic characterization of hMPV infections in children with lower ARI in Southern Brazil.     

Dopaminergic sensitivity and cocaine abuse: response to apomorphine

Ten male patients with chronic cocaine abuse received a single dose of the dopamine agonist apomorphine. Self-ratings of cocaine craving, depression, and anxiety decreased in response to apomorphine. Neuroendocrine response was consistent with central dopaminergic stimulation. Patients in the "craving" phase of the cocaine abuse cycle differed in behavioral but not neuroendocrine response to apomorphine from patients in the "crash" phase. Decrease in cocaine craving correlated with decrease in plasma homovanillic acid (pHVA). Total cocaine consumption correlated negatively with baseline prolactin and pHVA levels and inversely with peak change in prolactin following apomorphine. Patients had blunted neuroendocrine response to apomorphine in comparison to historical normal controls. Implications for the "dopamine" hypothesis of cocaine abuse are discussed.     

Cardiac evaluation in children with suspected heart disease. Preliminary results in 2000 patients

Two thousand consecutive children have been evaluated for suspected heart disease in a 27-month period. The main reasons for referral were: murmur (70%), precordial pain (9.5%), suspicion of arrhythmia (8.5%) and breathless (5%). Five hundred and six (25%) cases did not complete the investigation and the results were not computed. A final diagnosis was obtained based on the reason for referral and the main conclusions were: 1) a high incidence of normality was found: murmur (83%), pain (98%), arrhythmia (97%) and breathless (94%); 2) heart disease is unlikely when other referral reasons were analyzed; 3) 14% of the children were considered abnormal and the necessity of therapeutic procedures was 0.8%. A pediatric cardiology outpatient clinic in a public setting seems to be justifiable in the region, due to the high current demand.     

Congenital intramedullary tumor with neonatal manifestations

The authors report on a 45-day-old boy with a congenital intramedullary tumor with clinical manifestations since birth. Neurologic examination disclosed severe bilateral lower-limb hypotonia and diplegia, with exacerbated deep tendon reflexes and clonus associated with severe pain at manipulation. Further evaluation of this patient included screening for infections, computed tomographic scan, myelography, and somatosensory evoked potentials. The definite diagnosis was a solid holocord astrocytoma. This report discusses a rare disorder in the neonatal period and makes other medical practitioners aware of this diagnosis. Previously published literature is also reviewed.     

The use of genetic instability as a clinical tool for cancer diagnosis

Human tumors exhibit two fundamentally important characteristics, extensive genetic alteration and clonality. Although it is still unclear to what extent tumors have an elevated mutational burden as compared with normal tissue, their clonality results in their ready detection. Thus, assaying tissues for clonal alterations at frequently mutated microsatellite loci represents a viable approach to cancer diagnosis. The most remarkable extension of this concept is that not only can cancer cells be detected in biological samples, but tumor DNA can also be directly detected in the serum or plasma of patients with some forms of cancer. This recent finding is currently being explored but may represent an important contribution to future diagnostic strategies.     

An assessment of fructose-1,6-bisphosphate as an antimicrobial and anti-inflammatory agent in sepsis.

Tissue lesion mechanisms provoked by sepsis include the infectious process, inflammation, and cellular energy deficit. We chose to test fructose-1,6-bisphosphate (FBP) because of its possible anti-inflammatory and antimicrobial actions. Wistar rats were used and divided into three experimental groups: a control group (n=10), in which a capsule was introduced into the peritoneum of the animals; a septic group (n=10), in which a capsule containing non-sterile fecal matter was introduced together with Escherichia coli (1.5 x 10(9)CFU); and a septic group treated with FBP 500 mg/kg (n=10). The blood cell tests revealed that levels of leukocytes increased significantly in the septic group when compared to both the septic group treated with FBP and the control group. The blood cultures were 100% positive in both the septic group and the septic group treated with bisphosphorylated sugar. The antibiogram only revealed an inhibitory halo in the case of the antibiotic ampicillin, there was no such indication for FBP. The anti-inflammatory power of FBP remained at 60% for 5 h in the rats that received the carrageenan injection. What is more, the sugar reduced the levels of ionic calcium in relation to the control group. This data proves the validity of using FBP in the treatment of sepsis, possibly due to its anti-inflammatory rather than antimicrobial action.     

Hérida Regina Nunes SALGADO,et al:Microbiological assay for the determination of azithromycin in ophthalmic solutionsMicrobiological assay for the determination of azithromycin in ophthalmic solutions

IntroductionAzithromyciniscommercializedbypharmaciesinBrazilinophthalmicsolutionform. Despitetheproveneffectivenessandsafetyinitstreatment, thisdrug,untilthen, doesnotpossessamethodologyofstandar dizedanalysisforophthalmicsolutionsinofficialcom pendiumsan…