A fertile male with cystic fibrosis: molecular genetic analysis.

A family study is presented in which the father of a girl with severe cystic fibrosis (CF) was also found to have CF but was mildly affected. He was diagnosed with three positive sweat tests including one after suppression with fludrocortisone. Genetic analysis showed that he is a compound heterozygote with the delta F508 CF mutation associated with haplotype B and a second CF mutation associated with haplotype C. In this unusual, fertile CF male, the late age of diagnosis (30 years) and the mild clinical picture suggest that the compound genotype (delta F508/other CF mutation) determines a much less severe form of the disease which might have gone unnoticed in the absence of a severely affected child. The implications of these findings for genetic counselling of families with CF are discussed.     

Microsatellite analysis of synchronous and metachronous tumors: a tool for double primary tumor and metastasis assessment.

Despite well-established histopathological features and the development of immunostaining of human neoplasms, there are a number of cases in which surgical pathologists cannot assure the origin of synchronous and metachronous tumors. In many cases, the classification of these lesions as either two separate primary tumors or as a single primary tumor with a metastasis has significant implications with respect to patient prognosis and recommendations for therapy. To establish the origin of tumors, we assessed tumor cell clonality using PCR-based microsatellite analysis on microdissected archival tissues for loss of heterozygosity (LOH) and microsatellite instability (MSI) in a series of 19 paired synchronous and metachronous tumors from several organs. As a control group, 15 autopsy cases with an unequivocally recognizable primary tumor and associated metastases were also examined. Based on LOH and MSI findings, and using a panel of 4 to 12 (median 7) microsatellite markers, we were able to establish the clonal pattern of microsatellite changes in 17 out of 19 (89%) biopsy cases and thus determine if they were either double primary tumors (41%) or metastases (59%). Of interest, identical or similar pattern of microsatellite abnormalities were detected in 15 primary tumors and corresponding metastasis from autopsies. Our results indicate that microsatellite analysis for LOH and MSI, as an expression of clonality, provides a useful tool to distinguish double primary neoplasms and metastases in synchronous and metachronous tumors.     

Characterization of a bovine collagen-hydroxyapatite composite scaffold for bone tissue engineering

Different biomaterials have been used as scaffolds for bone tissue engineering. Here we characterize a biomaterial composed of sintered (1100 degrees C) and powdered hydroxyapatite (HA) and type I collagen (Coll), both of bovine origin, designed for osteoconductive and osteoinductive scaffolds. Coll/HA proportions were 1/2.6 and 1/1 (wet weight), and particles sizes varied from 200 to 400 microm. Vv (volume density) and Sv (surface to volume density) for the HA particles in the composite ranged from 0.48 +/- 0.06 to 0.55 +/- 0.02 and 5.090 +/- 0.545 to 6.366 +/- 0.289 microm(-1), respectively. Due to the relatively small changes in Vv and Sv, a macroporosity could be characterized for the biocomposite. X-ray diffraction and infrared spectroscopy showed that the sintered bone was composed essentially of HA with minimum additional groups such as surface calcium hydroxide, surface and crystal water, free carbon dioxide and possibly brushite. Mass spectrometry detected carbonates at A and B sites of HA, and weakly bound to the structure. Human osteoblasts adhered and spread on both the HA particle surface and the collagen fibers, which seemed to guide cells between adjacent particles. The biocomposite studied has several characteristics considered as ideal for its use as a scaffold for osteoconduction and osteoinduction.     

Risk factors for asthma among children in Maputo (Mozambique)

BACKGROUND: Few studies have looked at risk factors for asthma in African children. We aimed to identify the risk factors associated with childhood asthma in Maputo (Mozambique). METHODS: This case-control study included 199 age-matched children (100 asthmatic and 99 nonasthmatic) who attended Maputo Central Hospital between January 1999 and July 2000. We collected information concerning their familial history of atopy, birth weight, environment and breast-feeding. Detailed information about morbidity and treatment was obtained for each asthmatic child. RESULTS: The children were aged between 18 months and 8 years; 60% were male. The asthmatic children were hospitalized more frequently than the nonasthmatic children (P < 0.0001). Most of the asthmatic children lived in the urban area of Maputo [odd ratio (OR) = 6.73, CI = 3.1-14.0, P < 0.0001], had a parental history of asthma (OR = 26.8, CI = 10.8-68.2, P < 0.0001) or rhinitis (OR = 4, CI = 1.2-13.3, P = 0.005), had at least parent who smoked and were weaned earlier than the nonasthmatic children (OR = 2.4, CI = 1.3-4.4, P < 0.001). CONCLUSION: Childhood asthma was strongly associated with a family history of asthma and rhinitis, the place of residence, having smokers as parents and early weaning from maternal breast milk. These results highlight the need to reassess the management of asthmatic children in Maputo.     

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.     

Laparoscopic pyeloplasty as an alternative to nephrectomy in adults with poorly functioning kidneys due to ureteropelvic junction obstruction

International Urology and Nephrology - To evaluate outcomes of laparoscopic pyeloplasty (LP) in adults with poorly functioning kidney due to ureteropelvic junction obstruction (UPJO). A...     

Exercise-induced signs of muscle overuse in children

Signs of overuse after intense muscular exertion are well described in adults, while little research has been conducted in children. The aim of the study was to investigate some indirect markers of muscle damage in 13 years old boys following two different protocols of one-leg stepping exercise to exhaustion. This stepping exercise was performed by two experimental groups with different contributions of concentric and eccentric contractions in a 1:1 vs 1:2 ratio of timing. Subjective soreness perception and maximum voluntary isometric force of the knee extensor muscles were measured immediately prior to and immediately following the exercise, and at 1, 3, 24, 48, 72, 96 hours post exercise. Metabolic markers of exercise stress were taken at similar time intervals and included plasma glutathione concentrations as a marker for oxidative stress, circulating leukocyte numbers, and plasma creatine kinase (CK) activity. All parameters studied demonstrated a higher level of muscular exertion, with more evident signs of overuse in the group with the more eccentric contribution. Complete recovery was achieved between 72 and 96 hours after exertion. However, in this group of boys, the CK activity did not show the typical adult-like increase. Therefore the wide use of CK as an indicator of intense muscle exertion was not supported in this group of children. It can be concluded that children, like adults, experience similar degrees of muscle disturbances following intense exercise and that they may recover more quickly from such exercise.     

Immunomodulatory effect of cimetidine on the proliferative responses of splenocytes from T. cruzi-infected rats.

The immunomodulatory effect of cimetidine (CIM), a histamine type-2 receptor antagonist, was evaluated in respect to the blastogenic response to Con A of Wistar Furth (WF) rats infected by the Y strain of Trypanosoma cruzi (T. cruzi). Enhancement of blastogenesis of normal splenocytes was observed at a concentration of 10(3) M. However, the splenocytes from infected animals responded to concentrations of CIM ranging from 10(-8) to 10(-3) M. The mitogenic response to Con A of cells from infected animals was restored in the presence of CIM. The results show that CIM modulates the "in vitro" proliferative response of cells from T. cruzi-infected rats and suggest an immunoregulatory role of histamine and/or of cells that express H2 receptors in this infection.