Do neuropsychiatric fluctuations temporally match motor fluctuations in Parkinson’s disease?

Neurological Sciences - In Parkinson’s disease (PD), non-motor fluctuations (NMFs), especially neuropsychiatric fluctuations, often coexist with motor fluctuations (MFs) but are often...     

Patient- and Provider-Reported Information about Transplantation and Subsequent Waitlisting

Because informed consent requires discussion of alternative treatments, proper consent for dialysis should incorporate discussion about other renal replacement options including kidney transplantation (KT). Accordingly, dialysis providers are required to indicate KT provision of information (KTPI) on CMS Form-2728; however, provider-reported KTPI does not necessarily imply adequate provision of information. Furthermore, the effect of KTPI on pursuit of KT remains unclear. We compared provider-reported KTPI (Form-2728) with patient-reported KTPI (in-person survey of whether a nephrologist or dialysis staff had discussed KT) in a prospective ancillary study of 388 hemodialysis initiates. KTPI was reported by both patient and provider for 56.2% of participants, by provider only for 27.8%, by patient only for 8.3%, and by neither for 7.7%. Among participants with provider-reported KTPI, older age was associated with lack of patient-reported KTPI. Linkage with the Scientific Registry for Transplant Recipients showed that 20.9% of participants were subsequently listed for KT. Patient-reported KTPI was independently associated with a 2.95-fold (95% confidence interval [95% CI], 1.54 to 5.66; P=0.001) higher likelihood of KT listing, whereas provider-reported KTPI was not associated with listing (hazard ratio, 1.18; 95% CI, 0.60 to 2.32; P=0.62). Our findings suggest that patient perception of KTPI is more important for KT listing than provider-reported KTPI. Patient-reported and provider-reported KTPI should be collected for quality assessment in dialysis centers because factors associated with discordance between these metrics might inform interventions to improve this process.     

Clinical isolation and functional characterization of cord blood CD133+ hematopoietic progenitor cells

BACKGROUND: Human cord blood is a relevant source of CD133+ HPCs. Clinical-scale isolation of human umbilical cord blood (UCB) CD133+ HPCs using immunomagnetic microbeads and the CliniMACS clinical cell isolator is reported. CD133+ HPCs isolated after large-scale processing were functionally characterized. STUDY DESIGN AND METHODS: Closed disposable sets were used to process nine different samples of RBC-reduced UCB nucleated cells. In-vitro hematopoietic assays and human xenografts in NOD/SCID mice were performed to assess the functional properties of isolated CD133+ cells. Different mixtures of human cytokines were tested for the ability to expand nascent CD133+ HPCs. Furthermore, freshly isolated CD133+ cells were conditioned in culture medium specifically tested to support in-vitro myogenesis or osteogenesis. RESULTS: Isolation procedures yielded the recovery of an average of 2.53 x 10(6) CD133+ HPCs with a mean recovery of 96 percent (referred to as RBC-reduced samples) and a final sample purity of 82 percent. Purified CD133+ cells had high cloning efficiency, had relevant long-term activity, and were capable of repopulating irradiated NOD/SCID mice. In 10-day stroma-free cultures, a 2-fold and 8.3-fold expansion of colony-forming cells (CFCs) and extended long-term culture-initiating cells, respectively, was obtained. Freshly isolated CD133+ cells differentiated into large nucleated cells expressing either myosin D or osteopontin (as revealed by RT-PCR and immuno-cytochemistry), with a protein/mRNA expression comparable to or even higher than that observed in UCB CD133- nucleated cells in identical culture conditions. CONCLUSION: Collectively, clinical-scale isolation of UCB CD133+ cells provides a relevant amount of primitive HPCs with high hematopoietic activity and in-vitro mesenchymal potential.     

Genome-wide scans for diabetic nephropathy and albuminuria in multiethnic populations: the family investigation of nephropathy and diabetes (FIND)

The Family Investigation of Nephropathy and Diabetes (FIND) was initiated to map genes underlying susceptibility to diabetic nephropathy. A total of 11 centers participated under a single collection protocol to recruit large numbers of diabetic sibling pairs concordant and discordant for diabetic nephropathy. We report the findings from the first-phase genetic analyses in 1,227 participants from 378 pedigrees of European-American, African-American, Mexican-American, and American Indian descent recruited from eight centers. Model-free linkage analyses, using a dichotomous definition for diabetic nephropathy in 397 sibling pairs, as well as the quantitative trait urinary albumin-to-creatinine ratio (ACR), were performed using the Haseman-Elston linkage test on 404 microsatellite markers. The strongest evidence of linkage to the diabetic nephropathy trait was on chromosomes 7q21.3, 10p15.3, 14q23.1, and 18q22.3. In ACR (883 diabetic sibling pairs), the strongest linkage signals were on chromosomes 2q14.1, 7q21.1, and 15q26.3. These results confirm regions of linkage to diabetic nephropathy on chromosomes 7q, 10p, and 18q from prior reports, making it important that genes underlying these peaks be evaluated for their contribution to nephropathy susceptibility. Large family collections consisting of multiple members with diabetes and advanced nephropathy are likely to accelerate the identification of genes causing diabetic nephropathy, a life-threatening complication of diabetes.     

Blood pressure change and risk of hypertension associated with parental hypertension: the Johns Hopkins Precursors Study

BACKGROUND: Parental hypertension is used to classify hypertension risk in young adults, but the long-term association of parental hypertension with blood pressure (BP) change and risk of hypertension over the adult life span has not been well studied. METHODS: We examined the association of parental hypertension with BP change and hypertension risk from young adulthood through the ninth decade of life in a longitudinal cohort of 1160 male former medical students with 54 years of follow-up. RESULTS: In mixed-effects models using 29 867 BP measurements, mean systolic and diastolic BP readings were significantly higher at baseline among participants with parental hypertension. The rate of annual increase was slightly higher for systolic (0.03 mm Hg, P= .04), but not diastolic, BP in those with parental hypertension. After adjustment for baseline systolic and diastolic BP and time-dependent covariates--body mass index, alcohol consumption, coffee drinking, physical activity, and cigarette smoking--the hazard ratio (95% confidence interval [CI]) of hypertension development was 1.5 (1.2-2.0) for men with maternal hypertension only, 1.8 (1.4-2.4) for men with paternal hypertension only, and 2.4 (1.8-3.2) for men with hypertension in both parents compared with men whose parents never developed hypertension. Early-onset (at age 相似文献   

Life‐Sustaining Treatments: What Do Physicians Want and Do They Express Their Wishes to Others?

OBJECTIVES: To assess whether older physicians have discussed their preferences for medical care at the end of life with their physicians, whether they have established an advance directive, and what life-sustaining treatment they wish in the event of incapacity to make these decisions for themselves. DESIGN: Mailed survey to a cohort of physicians. SETTING: Physicians who were medical students at the Johns Hopkins University in graduating classes from 1946 to 1964. PARTICIPANTS: Physicians who completed the advance directive questionnaire (mean age 68). MEASUREMENTS: Questionnaires were sent out to known surviving physicians of the Precursors Study, an on-going study that began in 1946, asking physicians about their preferences for life-sustaining treatments. RESULTS: Of 999 physicians who were sent the survey, 765 (77%) responded. Forty-six percent of the physicians felt that their own doctors were unaware of their treatment preferences or were not sure, and of these respondents, 59% had no intention of discussing their wishes with their doctors within the next year. In contrast, 89% thought their families were probably or definitely aware of their preferences. Sixty-four percent reported that they had established an advance directive. Compared with physicians without advance directives, physicians who established an advance directive were more likely to believe that their doctors (odds ratio (OR) = 3.42, 95% confidence interval (CI) = 2.49-4.69) or family members (OR = 9.58, 95% CI = 5.33-17.23) were aware of their preferences for end-of-life care and were more likely to refuse treatments than those without advance directives. CONCLUSION: This survey of physicians calls attention to the gap between preferences for medical care at the end of life and expressing wishes to others through discussion and advance directives, even among physicians.     

Prospective association between hypotension and idiopathic chronic fatigue

OBJECTIVE: To determine whether there is an association between hypotension and incident cases of idiopathic chronic fatigue. DESIGN: A prospective study. SETTING: Johns Hopkins Precursors Study. PARTICIPANTS: Medical students (n = 876) in graduating classes from 1948 to 1964. MAIN OUTCOME MEASURE: 'Easy fatigability' reported by participants at 5- or 10-year follow-up after graduation. RESULTS: The unadjusted risk in women was 5.0 (95% exact confidence interval = 1.4 to 17.4) and in men was 1.7 (95% exact confidence interval = 0.8, to 3.5). CONCLUSION: These preliminary findings suggest that hypotension may be a risk factor for the development of idiopathic chronic fatigue in women.     

Approach to discover T- and B-cell antigens of intracellular pathogens applied to the design of Chlamydia trachomatis vaccines

Natural immunity against obligate and/or facultative intracellular pathogens is usually mediated by both humoral and cellular immunity. The identification of those antigens stimulating both arms of the immune system is instrumental for vaccine discovery. Although high-throughput technologies have been applied for the discovery of antibody-inducing antigens, few examples of their application for T-cell antigens have been reported. We describe how the compilation of the immunome, here defined as the pool of immunogenic antigens inducing T- and B-cell responses in vivo, can lead to vaccine candidates against Chlamydia trachomatis. We selected 120 C. trachomatis proteins and assessed their immunogenicity using two parallel high-throughput approaches. Protein arrays were generated and screened with sera from C. trachomatis-infected patients to identify antibody-inducing antigens. Splenocytes from C. trachomatis-infected mice were stimulated with 79 proteins, and the frequency of antigen-specific CD4(+)/IFN-γ(+) T cells was analyzed by flow cytometry. We identified 21 antibody-inducing antigens, 16 CD4(+)/IFN-γ(+)-inducing antigens, and five antigens eliciting both types of responses. Assessment of their protective activity in a mouse model of Chlamydia muridarum lung infection led to the identification of seven antigens conferring partial protection when administered with LTK63/CpG adjuvant. Protection was largely the result of cellular immunity as assessed by CD4(+) T-cell depletion. The seven antigens provided robust additive protection when combined in four-antigen combinations. This study paves the way for the development of an effective anti-Chlamydia vaccine and provides a general approach for the discovery of vaccines against other intracellular pathogens.