Analysis of the strain relatedness of oral Candida albicans in patients with diabetes mellitus using polymerase chain reaction‐fingerprinting

To increase our understanding of Candida pathogenicity, the identification of those strains most frequently associated with infections is of paramount importance. Polymerase chain reaction (PCR)‐based methods are extremely effective in differentiating and determining reproducibility, they require minimum starting material and are rapid and simple to perform. In this study, the genetic relatedness of Candida albicans was assessed for two geographically different patient groups (London, UK and Parma, Italy) affected by diabetes mellitus. C. albicans samples from the oral cavities of non‐diabetic healthy subjects were also examined by PCR fingerprinting to evaluate the possible genetic differences among endogenous strains in individuals with and without diabetes mellitus. PCR fingerprinting, with subsequent phylogenetic analysis of C. albicans isolates from the diabetic patients from London and Italy and from the non‐diabetic subjects, revealed that there were significant differences (P < 0.0001) between C. albicans isolates indicative of the distinct ecological niches that occur in the oral cavities of these patient cohorts. The most diverse group comprised the isolates from the diabetic patients in the UK, possibly reflecting the antifungal treatment that these patients had received. Further studies that include isolates from patient cohorts with systemic diseases other than diabetes mellitus, and from more diverse geographic localities are required to explain the relatedness of C. albicans isolates in the mouth.     

Cerebral autoregulation is preserved in multiple system atrophy: A transcranial Doppler study.

Patients with multiple system atrophy (MSA) present large changes in blood pressure (BP) due to autonomic disturbances. We analyzed how this change may influence dynamic cerebral autoregulation (DCA). Simultaneous recordings of arterial BP (Finapres) and middle cerebral artery (MCA) blood flow velocity (BFV) (transcranial Doppler) were performed in 10 patients with MSA (61 +/- 12 yr of age) and 12 healthy volunteers (61 +/- 11 yr of age): cerebral BFV response to oscillations in mean BP was studied in the supine position by cross-spectral analysis of mean BP and mean MCA BFV. The DCA was also studied during the decrease in BP the first seconds when standing up from a sitting position by the assessment of the cerebrovascular resistance index (CR; mean BP/mean MCA BFV ratio). The MCA BFV/BP cross-spectral analysis showed a phase for the mid-frequency band (0.07-0.2 Hz) significantly larger in MSA, suggesting more active autoregulation in response to larger changes in BP. Changes in CR reflecting the rate of autoregulation, when standing did not differ between the two groups. These data suggest that dynamic cerebral autoregulation is preserved in MSA.     

Evaluation of polymerase chain reaction and adenosine deaminase assay for the diagnosis of tuberculous effusions in children.

AIM: To evaluate and compare the utility of polymerase chain reaction (PCR) for the diagnosis of tuberculous effusions in children. METHODS: PCR, adenosine deaminase (ADA) activity and absolute lymphocyte count (ALC) were evaluated in the fluid of 31 tuberculous (20 pleural, 8 ascites and 3 pericardial) and 24 non-tuberculous (10 transudtative ascites, 8 empyema thoracis, 3 malignant pleural and 3 pyopericardium) effusions. RESULTS: Fluid PCR for Mycobacterium tuberculosis was positive in 74% of tuberculous effusions, whereas it was falsely positive in 13% of the non-tuberculous group. The mean fluid ADA and ALC values were significantly higher in tuberculous effusions than in non-tuberculous effusions (p<0.001). The sensitivity and specificity of PCR, ADA (> or =38 IU/l) and ALC (> or =275/mm3) were 74% and 88%, 81% and 75%, and 90% and 83%, respectively, in diagnosing tuberculous effusions. The sensitivity of PCR, ADA and ALC was 100%, 100% and 88%, respectively, for confirmed tuberculous effusions. When the two tests were combined (either/or positive), the sensitivity increased (90-100%) at the expense of specificity. When both the tests were positive, then the specificity markedly increased (92-96%), but sensitivity of the tests decreased. CONCLUSION: Fluid PCR alone should not be relied on as a single test; rather, combined analysis with either ADA or ALC could be more useful in the diagnosis of tuberculous effusions in children.     

Measurement of kinetic parameters in skeletal muscle by magnetic resonance imaging with an intravascular agent.

The purpose of this work was to investigate the use of an intravascular contrast agent to determine perfusion kinetics in skeletal muscle. A two-compartment kinetic model was used to represent the flux of contrast agent between the intravascular space and extravascular extracellular space (EES). The relationship between the image signal-to-noise ratio (SNR) and errors in estimating permeability surface area product (Ktrans), interstitial volume (ve), and plasma volume (vp) for linear and nonlinear curve-fitting methods was estimated from Monte Carlo simulations. Similar results were obtained for both methods. For an image SNR of 60, the estimated errors in these parameters were 10%, 22%, and 17%, respectively. In vivo experiments were conducted in rabbits to examine physiological differences between these parameters in the soleus (SOL) and tibialis anterior (TA) muscles in the hind limb. Values for Ktrans were significantly higher in the SOL (3.2+/-0.9 vs. 2.0+/-0.5x10(-3) min-1), as were values for vp (3.4+/-0.8 vs. 2.1+/-0.7%). Differences in ve for the two muscles (8.7+/-2.2 vs. 8.5+/-1.6%) were not found to be significant. These results demonstrate that relevant physiological metrics can be calculated in skeletal muscle using MRI with an intravascular contrast agent.     

无（外侧）额叶皮质是否更好？额叶病变患者解决洞察力问题

最近提出的关于额叶功能的理论认为前额叶皮质，尤其是其背外侧面在确定适合一项特殊任务的一系列反应中起重要作用，并在选择中使上述反应发生偏差。这些活动事实上是为任何类型的非常规任务而执行，而不考虑内容的差别。本研究旨在通过一项解决“洞察力”问题的测试任务（即火柴杆算术作业），来验证Frith“塑造反应空间”假说的预测效力。从Knoblich等人对健康人不能解决火柴杆问题的解释和Frith关于额叶背外侧皮质作用的理论，作者推导出与直觉相左的预测，即对这些相对复杂的任务，外侧额叶皮质局部损伤的患者可能比1组健康受试者完成得更好。要求35例经CT或MRI扫描证实为单个局部脑损伤的患者（年龄为26—65岁）和23例健康受试者（年龄为34—62岁）完成火柴杆作业。研究结果似乎与理论上的预测相一致，虽然仅有43％的健康受试者能解决最困难的火柴杆问题（“C类”），但是却有82％的额叶外侧损伤患者完成了类似问题（Fisher精确概率检验，P〈0．05）。总之，对Frith和Knoblich等人理论的结合进行了确证。     

Low level of response to alcohol as associated with serotonin transporter genotype and high alcohol intake in adolescents.

BACKGROUND: A low level of response to alcohol has been associated with both the genetic constitution of the regulatory region (SLC6A4) of the human serotonin (5-hydroxytryptamine, 5-HT) transporter (5-HTT) and with future alcohol intake and an increased risk for alcoholism. To date, all studies of relevant polymorphisms have been carried out in populations in the United States. METHODS: Data were extracted from a subset (n = 243) of a cohort of children who have been observed since birth through evaluation of the family history of alcoholism and psychosocial risk influences. At age 16 years, the response to alcohol was assessed with the Self-Rating of the Effects of Alcohol (SRE) questionnaire, and the average amount of alcohol intake per month was assessed during the prior 6 months. Additional variables that were measured included the 5-HTT genotype, externalizing behavior, and sociodemographic variables, such as gender and age. RESULTS: The level of response to alcohol was significantly lower among carriers of two long alleles of the 5-HTT regulatory region compared with carriers of one or two short alleles (Mann-Whitney U = 5225.0, p = .005). In a multiple regression analysis, the level of response to alcohol and externalizing behavior but not psychosocial factors significantly predicted the average amount of alcohol intake per month. CONCLUSIONS: This study demonstrates that, independent of the assessed psychosocial variables, the 5-HTT genotype correlated with the level of response to alcohol and predicted alcohol intake among 16-year-old adolescents.     

The impact of a nurse externship program on the transition process from graduate to registered nurse: Part III. recruitment and retention effects.

This is the third and final part of a series of articles that report the findings of a study that investigated the effects of a summer externship program on the transition into a professional role among nurses who participated in a summer nurse externship program at an acute care pediatric hospital. Specifically, this article reports the retention and recruitment benefits of a summer nurse externship program for the institution from 1998 through 2003. A total of 153 externs out of the 193 (79.0%) assumed a registered nurse position at the institution, and 77% remained in that role for 12 months. Overall, the nurse extern program for this institution appeared to be an effective recruitment and retention strategy that is on par with the institution and national data for retention and turnover data.     

Tacrolimus Combined with Two Different Dosages of Sirolimus in Kidney Transplantation: Results of a Multicenter Study

Tacrolimus combined with mycophenolate mofetil (MMF) is an effective regimen in kidney transplantation. This study compared the efficacy of combining tacrolimus and two different dosages of sirolimus with an established tacrolimus-MMF regimen. Each day in addition to tacrolimus, 325 patients received 2 mg sirolimus (TAC-SRL2 mg), 325 patients received 0.5 mg sirolimus (TAC-SRL0.5 mg) and 327 patients 1 g MMF (TAC-MMF). The initial tacrolimus dose was 0.2 mg/kg/day. Sirolimus patients received loading doses of 6 or 1.5 mg, and daily doses of 2 or 0.5 mg thereafter. Steroid administration was identical for all groups. The incidence of biopsy-proven acute rejection was lower in the TAC-SRL2 mg group (15.7%) compared with the TAC-SRL0.5 mg (25.2%, p = 0.003) and the TAC-MMF groups (22.3%, p = 0.036). Six-month graft survival was 91.0% (TAC-SRL2 mg), 92.6% (TAC-SRL0.5 mg) and 92.4% (TAC-MMF); the respective values for patient survival were 98.1%, 97.8% and 97.9%. Thirty-four patients (10.5%), 19 patients (5.8%) and 16 patients (4.9%) in the TAC-SRL2 mg, TAC-SRL0.5 mg and TAC-MMF groups, respectively, discontinued the study because of adverse events. Hyperlipemia was reported more often in the TAC-SRL2 mg group (24.0%) compared with 19.4% (TAC-SRL0.5 mg) and 11.0% (TAC-MMF; p < 0.05). Combining 2 mg sirolimus/day with tacrolimus results in lower rates of acute rejection, but a higher incidence of adverse events.     

Application of breast cancer risk prediction models in clinical practice.

Breast cancer risk assessment provides an estimation of disease risk that can be used to guide management for women at all levels of risk. In addition, the likelihood that breast cancer risk is due to specific genetic susceptibility (such as BRCA1 or BRCA2 mutations) can be determined. Recent developments have reinforced the clinical importance of breast cancer risk assessment. Tamoxifen chemoprevention as well as prevention studies such as the Study of Tamoxifen and Raloxifene are available to women at increased risk of developing breast cancer. In addition, specific management strategies are now defined for BRCA1 and BRCA2 mutation carriers. Risk may be assessed as the likelihood of developing breast cancer (using risk assessment models) or as the likelihood of detecting a BRCA1 or BRCA2 mutation (using prior probability models). Each of the models has advantages and disadvantages, and all need to be interpreted in context. We review available risk assessment tools and discuss their application. As illustrated by clinical examples, optimal counseling may require the use of several models, as well as clinical judgment, to provide the most accurate and useful information to women and their families.     

Using complexity theory to build interventions that improve health care delivery in primary care

Previous observational research confirms abundant variation in primary care practice. While variation is sometimes viewed as problematic, its presence may also be highly informative in uncovering ways to enhance health care delivery when it represents unique adaptations to the values and needs of people within the practice and interactions with the local community and health care system. We describe a theoretical perspective for use in developing interventions to improve care that acknowledges the uniqueness of primary care practices and encourages flexibility in the form of intervention implementation, while maintaining fidelity to its essential functions.