Definition of high risk individuals to optimise strategies for primary prevention of cardiovascular diseases

The identification of high risk individuals is one of the main goals of cardiovascular primary prevention and constitutes the basis for implementing actions oriented toward reducing modifiable risk factors at individual level, from changing life styles to drug interventions. The most appropriate method for identifying high risk individuals is the evaluation of their absolute global risk, a probability indicator of incidence, predictable on the basis of risk factor levels. Risk functions, derived from longitudinal studies, are used to identify persons at high probability to develop cardiovascular diseases. The appropriateness of the use of these risk functions depends upon the characteristics of the population that generated them and of individuals which they are applied to. Risk charts are simply absolute global risks calculated by classes of risk factors; risk scores are more precise evaluation derived from absolute global risks calculated by continuous levels of risk factors. Risk charts and scores are formed through the risk functions derived from different studies: Framingham, PROCAM (Munster), Seven Countries Study, SCORE and Progetto CUORE. A further chart has been created using the Framingham Study and adapted to the guidelines of New Zealand regarding the treatment of dyslipidemias and blood pressure. Major differences can be found in the availability of risk factors in men and women and in the use of fatal and non-fatal coronary and cerebrovascular events as end-points. All these studies use different diagnostic criteria for identification, classification and validation of events. The awareness of the risk charts differences is a key issue to refine tools for prevention of cardiovascular disease in populations with different probabilities of disease frequency.     

Three peroxisome proliferator-activated receptor isotypes from each of two species of marine fish

The cloning and characterization of cDNAs and genes encoding three peroxisome proliferator-activated receptor (PPAR) isotypes from two species of marine fish, the plaice (Pleuronectes platessa) and the gilthead sea bream (Sparus aurata), are reported for the first time. Although differences in the genomic organization of the fish PPAR genes compared with their mammalian counterparts are evident, sequence alignments and phylogenetic comparisons show the fish genes to be homologs of mammalian PPARalpha, PPARbeta/delta, and PPARgamma. Like their mammalian homologs, fish PPARs bind to a variety of natural PPAR response elements (PPREs) present in the promoters of mammalian or piscine genes. In contrast, the mRNA expression pattern of PPARs in the two fish species differs from that observed in other vertebrates. Thus, PPARgamma is expressed more widely in fish tissues than in mammals, whereas PPARalpha and beta are expressed similarly in profile to mammals. Furthermore, nutritional status strongly influences the expression of all three PPAR isotypes in liver, whereas it has no effect on PPAR expression in intestinal and adipose tissues. Fish PPARalpha and beta exhibit an activation profile similar to that of the mammalian PPAR in response to a variety of activators/ligands, whereas PPARgamma is not activated by mammalian PPARgamma-specific ligands. Amino acid residues shown to be critical for ligand binding in mammalian PPARs are not conserved in fish PPARgamma and therefore, together with the distinct tissue expression profile of this receptor, suggest potential differences in the function of PPARgamma in fish compared with mammals.     

Use of "<Emphasis Type="Italic">biokit</Emphasis>HSV-2 Rapid Assay" to improve the positive predictive value of Focus HerpeSelect HSV-2 ELISA

Background  

Commercially available assays to detect antibodies to the herpes simplex virus type 2 (HSV-2)-specific glycoprotein gG-2 have markedly improved serologic diagnosis of HSV-2 infection. However, even tests with high specificity can have low positive predictive values in low prevalence populations. HSV-2 is a chronic, life-long viral infection that requires both medical attention and potential alterations in health care strategy. As such, the concern for false positive diagnoses is high confirmatory testing is routine for other viral serologies such as HIV and hepatitis C. We evaluated such a strategy for HSV-2 serology by using an easily performed commercial test, biokitHSV-2 rapid test ("Biokit"; Biokit USA, Lexington MA) as a confirmatory test for the widely used gG-2 specific serology ("Focus;" HerpeSelect HSV-2 ELISA; Focus Diagnostics, Cypress CA).     

Identification of a novel splice site mutation in the human hairless gene underlying atrichia with papular lesions

Atrichia with Papular Lesions (APL) is a rare autosomal recessive disorder characterized by complete hair loss that begins shortly after birth with the development of papular lesions on various regions of the body. Since the establishment of hairless (HR) gene mutations as the cause of this disorder, several patients previously assumed to suffer from alopecia universalis have been subsequently diagnosed with APL. In this study we have identified a novel splicing mutation, IVS8+2T-->G, in the hairless gene. This mutation most likely abolishes normal splicing of exon 8 and potentially leads to out-of-frame skipping of this exon and a downstream premature termination codon (PTC). Our findings contribute to the growing body of HR mutations implicated in APL and provide further evidence for the differentiation of APL from alopecia universalis.     

Serotype distribution and antimicrobial susceptibility of <Emphasis Type="Italic"> Streptococcus pneumoniae </Emphasis>causing invasive infections and acute otitis media in children

A prospective study was conducted to determine the serotypes and antibiotic resistance patterns of pneumococcal isolates from children with invasive pneumococcal disease (IPD) and acute otitis media (AOM). From October 2001 to May 2002, 65 children with IPD (28 bacteraemic pneumonia, 24 bacteraemia without focus, 7 meningitis, 6 other infections) and 78 with AOM were identified. The most common serotypes causing IPD were 14 (32.3%), 6B (20.0%), 1 (18.5%) and 19F (7.7%) whereas the predominant serotypes causing AOM were 19F (35.9%), 14 (16.7%) and 23F (9.1%). Sixty-nine percent of IPD and 70.5% of AOM were caused by vaccine serotypes. The vaccine serotypes were more commonly encountered in meningitis cases and in children younger than 2 years of age. Intermediate resistance to penicillin was observed in 6 of 65 (9.2%) IPD isolates, one of which was intermediately resistant to cefotaxime (1.6%), whereas none exhibited high-level resistance to penicillin or other beta-lactam antibiotics. A higher proportion of antimicrobial resistance was noted in AOM isolates; 29 of 78 (37.4%) exhibited intermediate resistance and 8 (10.2%) high level resistance to penicillin, four of which had intermediate resistance to cefotaxime. Significant resistance was also noted to erythromycin; 38.5% of IPD and 48.7% of AOM isolates were resistant. Multidrug resistance was observed in one IPD and in eight AOM isolates. Conclusion:these findings have implications in the potential use of 7-valent conjugate vaccine in our region.Abbreviations AOM acute otitis media - IPD invasive pneumococcal disease - MIC minimal inhibitory concentration     

Obstetric characteristics and perinatal outcome of pregnancies with uterine leiomyomas

OBJECTIVE: To determine the rate, obstetric characteristics and perinatal outcome of pregnancies with uterine leiomyomas. STUDY DESIGN: A population-based study comparing all singleton deliveries between the years 1988 and 1999 in women with and without uterine leiomyomas was performed. Patients lacking prenatal care were excluded from the analysis. Multivariable analysis, adjusting for possible confounders, such as maternal age, parity and gestational age, was performed to investigate associations between uterine leiomyomas and selected outcomes. RESULTS: There were 105,909 singleton deliveries with 690 (0.65%) complicated by uterine leiomyomas during the study period. Using a multivariable analysis, the following conditions were significantly associated with uterine leiomyomas: nulliparity (odds ratio [OR]=4.0, 95% confidence interval [CI] 3.3-4.7, P<.001), chronic hypertension (OR=1.9, 95% CI 1.6-2.4, P<.001), hydramnios (OR=1.5, 95% CI 1.2-2.0, P<.001), diabetes mellitus (OR=1.4, 95% CI 1.1-1.7, P=.001) and advanced maternal age (OR=1.2, 95% CI 1.1-1.2, P<.001). Higher rates of perinatal mortality (2.2% vs. 1.2%, OR=1.8, 95% CI 1.1-3.2, P<.001) were found in the uterine leiomyoma group as compared to the control group. While adjusting for maternal age, parity, gestational age and malpresentation, pregnancies with uterine leiomyomas had higher rates of cesarean deliveries (OR=6.7, 95% CI 5.5-8.1, P<.001), placental abruption (OR=2.6, 95% CI 1.6-4.2, P<.001) and preterm deliveries (<36 weeks' gestation, OR=1.4, 95% CI 1.1-1.7, P=.009) as compared to pregnancies without uterine leiomyomas. Conversely, no significant differences were noted regarding perinatal mortality (OR=1.4, 95% CI 0.7-2.8, P=.351) after controlling for maternal age, parity and gestational age using a multivariable analysis. CONCLUSION: Uterine leiomyomas increase the risk of adverse pregnancy outcomes, thus emphasizing the importance of appropriate intrapartum management of these high-risk pregnancies.     

How medical students define surgical mentors

BACKGROUND: Current literature does not define ideal qualities of surgical mentors. We sought to define mentoring qualities desired by medical students in attending and resident surgeons. METHODS: We conducted a survey asking third-year medical students to identify the best attending surgeon and resident surgeon mentors during their surgical clerkship and to explain their selections. Comments were systematically evaluated using content analysis. RESULTS: The survey response rate was 94.8%. Attending surgeon mentors were described by 84 students; 70 students described resident surgeon mentors. Students most frequently described the "teacher" role for attending surgeons. For resident surgeon mentors, students most often ranked the "person" role. Students prioritized characteristics or attributes within roles differently for attending and resident surgeon mentors. CONCLUSIONS: Medical students' expectations of attending and resident surgeon mentors differ. Emphasis on behaviors consonant with identified characteristics may improve mentoring of medical students by surgeons and increase interest in surgical careers.     

Resource utilization and its management in splenic trauma

Background

This study compared resource utilization and its management for splenic injury at 2 level-I trauma centers and a pediatric referral center with other facilities in a state currently developing a trauma system.

Methods

Management strategy, length of stay, and total charges for children were compared among the pediatric referral center, trauma centers, and other facilities. Adult management, length of stay, and total charges were compared between trauma centers and other facilities.

Results

Nonoperative management was more frequent in children at the pediatric referral center than trauma centers or other facilities and was more common in adults at trauma centers than at other facilities. Mean length of stay and total charges for children were significantly greater at the pediatric referral center and trauma centers than at other facilities and for adults at trauma centers than at other facilities. Facility type was associated with length of stay and total charges when injury type and severity were controlled.

Conclusions

Nonoperative management of splenic injury is more common at trauma centers, and splenic trauma management may be more costly at trauma centers.     

Conservative management of hyperplastic and multicentric nephroblastomatosis

PURPOSE: The treatment of hyperplastic nephroblastomatosis remains controversial. We report the advantages of conservative management of hyperplastic and multicentric nephroblastomatosis associated with unilateral Wilms tumor (WT). MATERIALS AND METHODS: During the last 10 years 48 children with unilateral WT were consecutively treated at our 2 institutions. Children with multiple solid renal masses on imaging were treated with 2-drug chemotherapy until disappearance of the lesions. Stabilization or progression of the lesions despite chemotherapy, as well as heterogeneity of the lesions on imaging, prompted nephron sparing surgery (NSS). RESULTS: Three female infants (12, 13 and 20 months old, respectively) presented with multiple solid renal tumors at imaging. Despite chemotherapy, small and unilateral WT developed in 2 cases of hyperplastic nephroblastomatosis, which was excised. One of these infants subsequently presented with a small contralateral metachronous WT, which was excised. Both infants are disease-free with 2 normal kidneys at followup of 6 and 2 years, respectively. The third infant, who presented with unilateral multicentric WT and unilateral hyperplastic nephroblastomatosis nodules, was successfully treated with preoperative chemotherapy and enucleation of 5 tumors. Subsequently, nephrectomy was performed at another institution because the abnormal kidney outline due to NSS was misinterpreted as a recurrence of WT. She was lost to followup. CONCLUSIONS: Hyperplastic and multicentric nephroblastomatosis is not a rare lesion and is most often associated, either initially or subsequently, with WT. In some infants with multiple solid renal masses on imaging chemotherapy and for developing WT NSS may safely allow maximum sparing of the parenchyma of both kidneys.