Molecular classifiers for acute kidney transplant rejection in peripheral blood by whole genome gene expression profiling.

There are no minimally invasive diagnostic metrics for acute kidney transplant rejection (AR), especially in the setting of the common confounding diagnosis, acute dysfunction with no rejection (ADNR). Thus, though kidney transplant biopsies remain the gold standard, they are invasive, have substantial risks, sampling error issues and significant costs and are not suitable for serial monitoring. Global gene expression profiles of 148 peripheral blood samples from transplant patients with excellent function and normal histology (TX; n = 46), AR (n = 63) and ADNR (n = 39), from two independent cohorts were analyzed with DNA microarrays. We applied a new normalization tool, frozen robust multi-array analysis, particularly suitable for clinical diagnostics, multiple prediction tools to discover, refine and validate robust molecular classifiers and we tested a novel one-by-one analysis strategy to model the real clinical application of this test. Multiple three-way classifier tools identified 200 highest value probesets with sensitivity, specificity, positive predictive value, negative predictive value and area under the curve for the validation cohort ranging from 82% to 100%, 76% to 95%, 76% to 95%, 79% to 100%, 84% to 100% and 0.817 to 0.968, respectively. We conclude that peripheral blood gene expression profiling can be used as a minimally invasive tool to accurately reveal TX, AR and ADNR in the setting of acute kidney transplant dysfunction.

Independent associations between personality traits and clinical characteristics of depression.

Few studies have examined age of onset and chronicity of depression in the same subject sample. The present study sought to determine whether personality traits related to early onset depression were different from those related to chronic depression. We tested the associations between personality self-reports and clinical characteristics of depression by conducting multiple and logistic regression analyses to determine whether personality uniquely predicted clinical characteristics and whether clinical characteristics uniquely predicted personality, after adjusting for depression severity. We also analyzed data at 6-month follow-up to determine whether age of onset and chronicity maintained their associations with personality. The study found that low levels of positive personality traits had unique associations with chronicity of depression, whereas elevated levels of negative personality traits had unique associations with an earlier onset of depression. Furthermore, associations were generally maintained over time, suggesting that associations between personality and these depression subtypes are stable.

Incident hepatitis C virus in women with human immunodeficiency virus infection.

Individuals infected with human immunodeficiency virus type 1 (HIV-1) are frequently coinfected with hepatitis C virus (HCV). Acute HCV infection is often asymptomatic and poorly understood. We conducted a historical prospective study of HCV antibody and viremia in plasma samples obtained during 1994-1999 from a cohort of initially HIV-1-infected, HCV-uninfected women and from HIV-1-HCV-uninfected women. Twenty-two (1.5%) of 1517 experienced seroconversion. Of these, 14 (64%) truly acquired a new infection as assessed by enzyme immunoassay response and new-onset viremia. The incidence rate in HIV-1-infected women was 2.7 cases per 1000 person-years; it was 3.3 cases per 1000 person-years in HIV-1-seronegative women (relative risk, 1.21; P=.75). Acquisition of HCV was associated with any history of drug use (P<.01). Five of 12 viremic, seroconverting individuals cleared viremia. Incident HCV infection among HIV-1-infected and HIV-1-uninfected women was low. It was linked to drug use and commonly resolved.

Retention of women enrolled in a prospective study of human immunodeficiency virus infection: impact of race, unstable housing, and use of human immunodeficiency virus therapy.

Even though women and people of color represent an increasing proportion of US acquired immunodeficiency syndrome (AIDS) cases, few research studies include adequate representation of these populations. Here the authors describe recruitment and retention of a diverse group of human immunodeficiency virus (HIV)-infected and at risk HIV-uninfected women in a prospective study operating in six sites across the United States. Methods used to minimize loss to follow-up in this cohort are also described. For the first 10 study visits that occurred during a 5-year period between 1994 and 1999, the retention rate of participants was approximately 82%. In adjusted Cox analysis, factors associated with retention among all women were older age, African-American race, stable housing, HIV-infected serostatus, past experience in studies of HIV/AIDS, and site of enrollment. In an adjusted Cox analysis of HIV-infected women, African-American race, past experience in studies of HIV/AIDS, site of enrollment, and reported use of combination or highly active antiretroviral HIV therapy at the last visit were significantly associated with retention. In adjusted Cox analysis of HIV-uninfected study participants, only the site of enrollment was significantly associated with study retention. These results show that women with and at risk for HIV infection, especially African-American women, can be successfully recruited and retained in prospective studies.

Herpes simplex virus shedding and plasma human immunodeficiency virus RNA levels in coinfected women.

Asymptomatic herpes simplex virus (HSV) shedding was described in a cohort of human immunodeficiency virus (HIV)-infected women, and the association of HSV shedding with changes in plasma HIV RNA load was investigated. Genital, rectal, and oral swabs were obtained daily during a 4-week period for polymerase chain reaction and culture, and concomitant plasma specimens were drawn 3 times weekly for determination of HIV RNA load. During the study, 70% and 79% of subjects shed HSV from the oral cavity and genital area, respectively. Shedding of HSV occurred for a mean of 3.2 days for oral shedding and 5.4 days for genital shedding. Mean plasma HIV RNA loads during periods of HSV shedding and nonshedding and for periods 3 days after the cessation of shedding were compared; no significant differences were found (P=.74). In women who shed HSV, as evaluated by detection of virus, plasma HIV RNA load did not fluctuate with HSV shedding.

Preferential suppression of CXCR4-specific strains of HIV-1 by antiviral therapy.

To initiate infection, HIV-1 requires a primary receptor, CD4, and a secondary receptor, principally the chemokine receptor CCR5 or CXCR4. Coreceptor usage plays a critical role in HIV-1 disease progression. HIV-1 transmitted in vivo generally uses CCR5 (R5), but later CXCR4 (X4) strains may emerge; this shift heralds CD4+ cell depletion and clinical deterioration. We asked whether antiretroviral therapy can shift HIV-1 populations back to R5 viruses after X4 strains have emerged, in part because treatment has been successful in slowing disease progression without uniformly suppressing plasma viremia. We analyzed the coreceptor usage of serial primary isolates from 15 women with advanced disease who demonstrated X4 viruses. Coreceptor usage was determined by using a HOS-CD4+ cell system, biological and molecular cloning, and sequencing the envelope gene V3 region. By constructing a mathematical model to measure the proportion of virus in a specimen using each coreceptor, we demonstrated that the predominant viral population shifted from X4 at baseline to R5 strains after treatment. Multivariate analyses showed that the shift was independent of changes in plasma HIV-1 RNA level and CD4+ cell count. Hence, combination therapy may lead to a change in phenotypic character as well as in the quantity of HIV-1. Shifts in coreceptor usage may thereby contribute to the clinical efficacy of anti-HIV drugs.

The impact of true partnership between a university Level I trauma center and a community Level II trauma center on patient transfer practices.

OBJECTIVE: To examine the effect of a clinical and administrative partnership with an academic urban Level I trauma center on the patient transfer practices at a suburban/rural Level II center. METHODS: Data for 2 years before affiliation (PRE) abstracted from inpatient charts and the trauma registry were compared with that for 2 years after (POST). The following data were collected: number of, reason for, and destination and demographics of transfers. Chi(2) test and t test analyses were used; p < 0.05 defined significance; data are mean +/- SEM. RESULTS: Transfer rate increased from 4% PRE to 6.9% (p = 0.001) POST with no significant difference in age, Glasgow Coma Scale score, Injury Severity Score, or Revised Trauma Score. Repatriation occurred in 12.8% POST (none PRE). The current Level I facility accepted 1.8% of all transfers PRE and 36.4% POST (p = 0.0001). PRE/POST rates by reason are as follows: pediatric, 14.6%/9.0% (p = 0.04); intensive care unit, 0.4%/1.7% (p = 0.13); complex orthopedic, 100%/0% (p = 0.005); vascular, 50%/0% (p = 0.008); spinal cord injury, 100%/100%; and ophthalmologic, 0%/100% (p = 0.005). CONCLUSIONS: In this experience of Level I/II partnership (1) transfer patterns were altered, (2) select patient cohort transfers decreased (pediatric, complex orthopedic, vascular), whereas others increased (aortic work-up), and (3) repatriation rates were low.

Mandated training of professionals: a means for improving reporting of suspected child abuse.

Professionals who are legally required to report suspicions of child abuse and neglect to a child abuse hotline often do not do so. In 1988 the New York State Legislature passed a law requiring professionals to take a 2-hour course called Identification and Reporting Child Abuse and Maltreatment as a prerequisite for licensure. New York Society for the Prevention of Cruelty to Children has provided this training for more than 2,500 physicians, psychologists, psychiatrists, nurses, teachers, and other professionals. A question affecting training content and quality, as well as policy decisions by child welfare professionals, remains: whether failure to report is founded in professionals' ignorance of the law and procedures involved in reporting or in their inability to recognize indicators of child abuse and neglect. NYSPCC conducted a survey of 1,368 course participants to determine the extent to which information in the course was new to them. Results indicated that substantial numbers of professionals were not aware of indicators of abuse; nevertheless all professionals were more knowledgeable about abuse than they were about legal obligations and procedures for reporting. A surprising finding was that teachers were no more knowledgeable about indicators of abuse than were other professionals, though most abused children are of school age. These and other results strongly supported the need to train professionals about indicators of child abuse and about how to report them.

Pulmonary diffusing capacity as a predictor of performance in competitive swimming.

Pulmonary diffusing capacity has been noted by many investigators to be higher in championship swimmers than in average swimmers and in the non-swimming population. We measured pulmonary diffusing capacity (DLCO) and other parameters in 22 members of a collegiate swimming team and studied the relationship between pulmonary diffusing capacity and swimming performance. We also investigated change in lung function over a season of training and racing. Results suggested that while most good swimmers had above average diffusing capacities, there was no statistically significant difference in performance between those swimmers with high DLCO (greater than or equal to 110% predicted value) and those with a low DLCO (less than 100% predicted value). It was also determined that there was not a good correlation between performance (measured by either "best time" or "average time") and lung function (DLCO or VC).

Observing child abuse.

Evidence from a study conducted at the New York Foundling Hospital and Albert Einstein College of Medicine, as well as previous research by the investigators, shows that abusive mothers are insensitive to the moods and signals of their children. A quantitative analysis of videotaped interaction sequences of 12 mother-child dyads indicated that abusive mothers spend less time looking at their children, are less focused in their attention on them, barrage them with words and actions that are unmodulated by the child's response, are physically coercive, and spend more time issuing directives and orders than mothers from similar backgrounds who do not physically abuse their children. We suggest that child abuse is part of a complex interaction system characterized by lack of mutual attunement between caretaker and child, of which acts of physical violence are dramatic exemplars. These data support the view that in order to ameliorate parenting skills of abusive parents, interactive patterns that appear early in the caretaker-child relationship must be understood and addressed.

A multidisciplinary approach to the treatment of child abuse.

A multidisciplinary team of professionals and paraprofessionals provides an innovative therapeutic approach for the treatment of child abuse and neglect among a deprived and disadvantaged population of abusing mothers. The therapeutic approach stresses residential care for mother and child, behavior modification through corrective child care experiences, personality modifications through individual and group therapy, and environmental and social changes through staff assistance and education.