Matrix metalloproteinases-2 and -9 in cervical cancer: different roles in tumor progression

The incidence of uterine cervical cancer has increased slightly in Western countries, with an increase in relatively young women. Overexpression of matrix metalloproteinases (MMPs)-2 and -9 has turned out as a prognostic factor in many cancers. We compared the expression of the proteins MMP-2 and MMP-9 in cervical primary tumors with clinical outcome and risk factors of cervical cancer. One hundred sixty-one patients with cervical cancer treated in Ume? University Hospital or Sahlgrenska University Hospital, Sweden, between 1991 and 1995 were included in the study. Paraffin-embedded tissue samples obtained prior to treatment were examined immunohistochemically by specific antibodies for MMP-2 and MMP-9. Forty-two percent of the tumors were intensively positive for MMP-2 and 31% for MMP-9. Nineteen percent of the samples were intensively positive for both proteinases and 47% negative or weak for both. Overexpression of MMP-2 seemed to predict unfavorable survival under Kaplan-Meier analysis and in the multivariate analysis. Early sexual activity and low parity seemed to correlate to overexpression of MMP-2. MMP-9 was not associated with survival or sexual behavior. Intensive MMP-9 was noted in grade 1 tumors. We conclude that MMP-2 and MMP-9 have different roles in uterine cervical cancer. MMP-2 could be associated with aggressive behavior, but MMP-9 expression diminishes in high-grade tumors.     

Predictability of retroperitoneal lymph node metastasis by using clinicopathologic variables in surgically staged endometrial cancer

The purpose of this study was to predict lymphatic involvement in endometrial cancer using clinicopathologic variables of patients treated with surgical staging. Overall, 461 patients treated with an initial surgical staging procedure including complete pelvic-para-aortic lymphadenectomy were included. The mean number of resected lymph nodes was 27 (median 26; range 15-83), and 54 patients (12%) had lymphatic involvement. Of these patients, 32 had only pelvic, 15 had both pelvic and para-aortic, and 7 had isolated para-aortic metastases. In the multivariate analysis, deep myometrial invasion (P= 0.02), lymphvascular space invasion (P= 0.001), positive peritoneal cytology (P= 0.002), and cervical involvement (P= 0.003) predicted retroperitoneal lymph node metastasis (RLN) significantly. Two hundred seventy-four patients (59.4%) had at least one of these poor prognostic factors identified by multivariate analysis. In this patient population, 53 (19.3%) had lymphatic involvement compared to 1 patient in the group of 187 patients with low-risk criteria. Ninety-eight percent of patients with RLN were predicted by this model, and with the advent of accurate diagnostic techniques, 40% of patients could be saved from undergoing lymphadenectomy.     

The diagnostic utility of a genetics evaluation in children with pervasive developmental disorders.

PURPOSE: A genetics evaluation of children with pervasive developmental disorders (PDDs) identifies a diagnosis in 6% to 15% of cases. However, previous studies have not measured the incidence of genetic disorders among children with autistic-like features who do not necessarily meet the Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition criteria for PDD. METHODS: We identified 101 patients at our institution referred for PDD, autism, Asperger syndrome, or autistic features. Seventy-eight were males and 23 were females, giving a male-to-female ratio of 3.4:1. No diagnosis was identified on examination alone, although Rett syndrome was suspected in six females. Seventeen patients did not undergo any type of testing because of noncompliance. RESULTS: Of the remaining 84 patients analyzed, seven (8.3%) were found to have abnormalities on testing. Three chromosomal anomalies were found: one with 5p duplication, one with low-level mosaicism for trisomy 21, and one with an unbalanced 10;22 translocation. Three females were diagnosed with Rett syndrome after MECP2 analysis identified a disease-causing mutation. The remaining patient was found to have an elevated urine orotic acid, with a normal ammonia level, of unknown significance. CONCLUSION: On the basis of our series, the yield of a genetics evaluation in patients with features of PDD who do not necessarily meet the Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition criteria is 8.3%. Approximately half of these were the result of a chromosomal abnormality. Three cases of Rett syndrome were identified for which autistic behaviors are a well-described feature. These findings suggest that a high-resolution karyotype provides the greatest diagnostic yield for patients with autistic-like features. MECP2 analysis should be considered for females who present with autistic behaviors.     

European Committee on Antimicrobial Susceptibility Testing (EUCAST) Technical Notes on antimicrobial susceptibility testing

The main objectives of the European Committee on Antimicrobial Susceptibility Testing (EUCAST) are to harmonise breakpoints for antimicrobial agents in Europe, and to act as the breakpoint committee for the European Medicines Agency (EMEA) during the registration of new antimicrobial agents. Detailed EUCAST procedures for harmonising and setting breakpoints for antimicrobial agents are available on the EUCAST website. Beginning with the current issue, a series of EUCAST Technical Notes will be published in CMI, based on the rationale documents produced by EUCAST for each of the antimicrobial agents studied, with the aim of highlighting important background information underlying decisions on breakpoints made by EUCAST.     

Development and evaluation of a new PCR assay for detection of Pseudomonas aeruginosa D genotype

This report describes a new PCR-based assay for the detection of Pseudomonas aeruginosa genotype D in occupational saturation diving systems in the North Sea. This genotype has persisted in these systems for 11 years (1993-2003) and represents 18% of isolates from infections analysed during this period. The new PCR assay was based on sequences obtained after randomly amplified polymorphic DNA (RAPD)-PCR analysis of a group of isolates related to diving that had been identified previously by pulsed-field gel electrophoresis (PFGE). The primer set for the D genotype targets a gene that codes for a hypothetical class 4 protein in the P. aeruginosa PAO1 genome. A primer set able to detect P. aeruginosa at the species level was also designed, based on the 23S-5S rDNA spacer region. The two assays produced 382-bp and 192-bp amplicons, respectively. The PCR assay was evaluated by analysing 100 P. aeruginosa isolates related to diving, representing 28 PFGE genotypes, and 38 clinical and community P. aeruginosa isolates and strains from other species. The assay identified all of the genotype D isolates tested. Two additional diving-relevant genotypes (TP2 and TP27) were also identified, as well as three isolates of non-diving origin. It was concluded that the new PCR assay is a useful tool for early detection and prevention of infections with the D genotype.     

Association between commensal bacteria and opportunistic pathogens in the dental plaque of elderly individuals

Opportunistic infections in the oral cavity of the elderly may increase the incidence of systemic disease. The objective of this study was to investigate the differences in the oral bacterial flora between dependent elderly (inpatients) and independent elderly (community-dwelling residents). After multiple variables were taken into account, inpatients had significantly lower detection rates than community-dwelling residents for alpha-streptococci (p < 0.001) and Neisseria (p 0.004), and higher detection rates for Pseudomonas aeruginosa (p 0.024), methicillin-resistant Staphylococcus aureus (MRSA) (p 0.011) and Actinomyces spp. (p 0.005). Among inpatients, the requirement for a high degree of care was related negatively to detection of alpha-streptococci, but was related significantly to detection of P. aeruginosa (p 0.018) or MRSA (p 0.004). Tube-fed inpatients had a significantly lower detection rate for alpha-streptococci (p 0.041) and a higher detection rate for P. aeruginosa (p 0.004) than those who did not require tube feeding. Inpatients with a history of antibiotic use had a significantly lower detection rate for alpha-streptococci (p 0.049) and a higher detection rate for MRSA (p 0.007) than those without a history of antibiotic use. The detection rates for P. aeruginosa or MRSA in inpatients without alpha-streptococci were higher than in inpatients with alpha-streptococci after controlling for age and gender (P. aeruginosa, p 0.006; MRSA, p 0.001). Overall, detection of alpha-streptococci had an inverse correlation with the detection of P. aeruginosa and MRSA in the oral cavity and is likely to be an indicator of pathogenic bacterial infection.     

Hood versus mask nebulization in infants with evolving bronchopulmonary dysplasia in the neonatal intensive care unit.

OBJECTIVE: To compare infants' discomfort, nursing-time and caregiver preference, and assess the clinical efficiency (as a secondary outcome) of hood versus facemask nebulization in infants with evolving bronchopulmonary dysplasia (BPD) in the neonatal intensive care unit. STUDY DESIGN: A prospective, open, randomized, controlled crossover clinical trial. In total, 10 infants with BPD who were on inhaled beta-agonist bronchodilators and corticosteroids were randomly assigned to receive their nebulized treatments either by a facemask, or by a hood for 2-3 days, and then crossover to receive the same treatments with the other technique for another 2-3 days. Infants' discomfort, nursing-time, caregiver preference and clinical efficiency were compared. RESULTS: At baseline there was no significant clinical difference between the groups. Nurse-time required for administering the hood nebulization (mean+/-s.e.m.: 1.9+/-0.1 min) was significantly shorter than the time for mask nebulization (12.0+/-0.6 min, P<0.0001). Infants' discomfort score was significantly lower (0.1+/-0.04) for hood versus mask nebulization (2.5+/-0.2, P<0.0001). Nurses and parents unequivocally preferred the hood treatment. During both mask and hood nebulization therapies (2-3 days) clinical efficiency was comparable. While both methods caused an immediate (20 min post) clinical improvement, the immediate respiratory assessment change score was significantly greater for the hood versus the mask nebulization (0.62+/-0.27 versus 0.13+/-0.14, P<0.05). CONCLUSIONS: Nebulization of aerosolized medications in infants with evolving BPD by hood was less time-consuming for caregivers and was much better tolerated by the infants while being at least as effective as the conventional facemask nebulization.     

Complete maternal uniparental isodisomy of chromosome 4 in a subject with major depressive disorder detected by high density SNP genotyping arrays.

Uniparental isodisomy (iUPD) is a rare genetic condition caused by non-disjunction during meiosis that ultimately leads to a duplication of either the maternal or paternal chromosome in the affected individual. Two types of disorders can result, those due to imprinted genes and those due to homozygosity of recessive disease-causing mutations. Here, we describe the third known case of complete chromosome 4 iUPD of maternal origin. This condition became apparent during whole genome linkage studies of psychiatric disorders in the Portuguese population. The proband is an adult female with normal fertility and no major medical complaints, but a history of major depressive disorder and multiple suicide attempts. The proband's siblings and parents had normal chromosome 4 genotypes and no history of mood disturbance. A brief review of other studies lends support for the possibility that genes on chromosome 4 might confer risk for mood disorders. We conclude that chromosome 4 maternal uniparental disomy (UPD) is a rare disorder that may present with a major depressive phenotype. The lack of a common disease phenotype between this and two other cases of chromosome 4 iUPD [Lindenbaum et al. [1991] Am J Med Genet 49(Suppl 285):1582; Spena et al. [2004] Eur J Hum Genet 12:891-898) would suggest that there is no vital maternal gene imprinting on chromosome 4. However, since there is no reported case of paternal chromosome 4 UPD, paternal gene imprinting on chromosome 4 cannot be excluded.