Antibody seronegative human T-lymphotropic virus type III (HTLV-III)- infected patients with acquired immunodeficiency syndrome or related disorders

The human T-lymphotropic virus type III (HTLV-III) is the primary cause of the acquired immunodeficiency syndrome (AIDS) and related disorders (ARC). Prior studies have reported that nearly all symptomatic patients with AIDS or ARC manifest antibody to HTLV-III. This observation has engendered efforts to screen for HTLV-III, especially prior to blood donation, with assays for antibody to HTLV-III. We report the first two cases, one with AIDS and one with ARC, that are HTLV-III virus positive but antibody negative. Accurate diagnosis of HTLV-III infection in some cases may require direct virus culture or tests for antigen. In addition, lack of HTLV-III antibody may indicate an atypical clinical course of AIDS.     

Deficits in hippocampal‐dependent transfer generalization learning accompany synaptic dysfunction in a mouse model of amyloidosis

Elevated β‐amyloid and impaired synaptic function in hippocampus are among the earliest manifestations of Alzheimer's disease (AD). Most cognitive assessments employed in both humans and animal models, however, are insensitive to this early disease pathology. One critical aspect of hippocampal function is its role in episodic memory, which involves the binding of temporally coincident sensory information (e.g., sights, smells, and sounds) to create a representation of a specific learning epoch. Flexible associations can be formed among these distinct sensory stimuli that enable the “transfer” of new learning across a wide variety of contexts. The current studies employed a mouse analog of an associative “transfer learning” task that has previously been used to identify risk for prodromal AD in humans. The rodent version of the task assesses the transfer of learning about stimulus features relevant to a food reward across a series of compound discrimination problems. The relevant feature that predicts the food reward is unchanged across problems, but an irrelevant feature (i.e., the context) is altered. Experiment 1 demonstrated that C57BL6/J mice with bilateral ibotenic acid lesions of hippocampus were able to discriminate between two stimuli on par with control mice; however, lesioned mice were unable to transfer or apply this learning to new problem configurations. Experiment 2 used the APP_swePS1 mouse model of amyloidosis to show that robust impairments in transfer learning are evident in mice with subtle β‐amyloid‐induced synaptic deficits in the hippocampus. Finally, Experiment 3 confirmed that the same transfer learning impairments observed in APPswePS1 mice were also evident in the Tg‐SwDI mouse, a second model of amyloidosis. Together, these data show that the ability to generalize learned associations to new contexts is disrupted even in the presence of subtle hippocampal dysfunction and suggest that, across species, this aspect of hippocampal‐dependent learning may be useful for early identification of AD‐like pathology. © 2015 Wiley Periodicals, Inc.     

PTSD in Asylum‐Seeking Male Adolescents From Afghanistan

This study concerned the mental health of Afghan unaccompanied asylum‐seeking children in the United Kingdom (UK). Afghans are the largest group of children seeking asylum in the UK, yet evidence concerning their mental health is limited. This study presents an estimate of probable posttraumatic stress disorder (PTSD) within this group and describes its associations with the cumulative effect of premigration traumatic events, immigration/asylum status, and social care living arrangements. Male adolescents (N = 222) aged 13–18 years completed validated self‐report screening measures for traumatic experiences and likely PTSD. One‐third (34.3%) scored above a selected cutoff, suggesting that they are likely to have PTSD. A higher incidence of premigration traumatic events was associated with greater PTSD symptomatology. Children living in semi‐independent care arrangements were more likely to report increased PTSD symptoms when compared to their peers in foster care. A substantial majority in this study did not score above the cutoff, raising the possibility of notable levels of resilience. Future research should consider approaching mental health issues from a resilience perspective to further the understanding of protective mechanisms for this at‐risk population.     

Pulmonary surfactant dysfunction in pediatric cystic fibrosis: Mechanisms and reversal with a lipid-sequestering drug

Background

Airway surfactant is impaired in cystic fibrosis (CF) and associated with declines in pulmonary function. We hypothesized that surfactant dysfunction in CF is due to an excess of cholesterol with an interaction with oxidation.

Kidney Transplantation in Previous Heart or Lung Recipients

Outcomes after heart and lung transplants have improved, and many recipients survive long enough to develop secondary renal failure, yet remain healthy enough to undergo kidney transplantation. We used national data reported to United Network for Organ Sharing (UNOS) to evaluate outcomes of 568 kidney after heart (KAH) and 210 kidney after lung (KAL) transplants performed between 1995 and 2008. Median time to kidney transplant was 100.3 months after heart, and 90.2 months after lung transplant. Renal failure was attributed to calcineurin inhibitor toxicity in most patients. Outcomes were compared with primary kidney recipients using matched controls (MC) to account for donor, recipient and graft characteristics. Although 5-year renal graft survival was lower than primary kidney recipients (61% KAH vs. 73.8% MC, p < 0.001; 62.6% KAL vs. 82.9% MC, p < 0.001), death-censored graft survival was comparable (84.9% KAH vs. 88.2% MC, p = 0.1; 87.6% KAL vs. 91.8% MC, p = 0.6). Furthermore, renal transplantation reduced the risk of death compared with dialysis by 43% for KAH and 54% for KAL recipients. Our findings that renal grafts function well and provide survival benefit in KAH and KAL recipients, but are limited in longevity by the general life expectancy of these recipients, might help inform clinical decision-making and allocation in this population.     

The effect of metabolic syndrome components on exercise performance in patients with intermittent claudication

PURPOSE: To determine the effect of metabolic syndrome components on intermittent claudication, physical function, health-related quality of life, and peripheral circulation in patients with peripheral arterial disease (PAD), and to identify the metabolic syndrome components most predictive of each outcome measure. METHODS: Patients limited by intermittent claudication with three (n = 48), four (n = 45), or five (n = 40) components of metabolic syndrome were studied. Patients were assessed on PAD-specific measures consisting of ankle-brachial index (ABI), initial claudication distance, absolute claudication distance, physical function measures, health-related quality of life, and calf blood flow and transcutaneous oxygen tension responses after 3 minutes of vascular occlusion. RESULTS: Initial claudication distance (mean +/- SD) progressively declined (P = .019) in those with three (203 +/- 167 m), four (124 +/- 77 m), and five (78 +/- 57 m) metabolic syndrome components, and absolute claudication distance progressively declined (P = .036) in these groups as well (414 +/- 224 m vs 323 +/- 153 m vs 249 +/- 152 m, respectively). Furthermore, compared with patients with only three components of metabolic syndrome, those with all five components had impaired values (P < .05) for peak oxygen uptake, ischemic window, 6-minute walk distance, self-perceived walking ability and health, daily physical activity, health-related quality of life on six of eight domains, calf hyperemia, and calf ischemia after vascular occlusion. Abdominal obesity was the predictor (P < .05) of exercise performance during the treadmill and 6-minute walk tests, as well as physical activity. Elevated fasting glucose was the predictor (P < .05) of peripheral vascular measures, self-perceived walking ability and health, and health-related quality of life. CONCLUSION: PAD patients with more metabolic syndrome components have worsened intermittent claudication, physical function, health-related quality of life, and peripheral circulation. Abdominal obesity and elevated fasting glucose are the metabolic syndrome components that are most predictive of these outcome measures. Aggressively treating these metabolic syndrome components may be particularly important in managing symptoms and long-term prognosis of PAD patients.     

Survival after gastric adenocarcinoma resection: Eighteen-year experience at a single institution

Gastric adenocarcinoma is the second leading cause of cancer death worldwide. In Western series, survival rates vary widely and are generally lower than those reported from Eastern series. We performed a retrospective analysis of cases operated on at the Johns Hopkins Hospital over the past 18 years and collected data on demographics, tumor characteristics, pathologic stage, treatment methods, complications, survival time, and other relevant factors. Survival according to stage of disease, Lauren tumor type, tumorlocation,time period, andadministration of adjuvant therapy wasanalyzed, andresultswerecompared with those of other Western series. During this period, 436 patients with gastric adenocarcinoma underwent resection. We have shown a statistically significant association between survival and margin status, stage of disease, and Lauren tumor type. Overall 5-year survival was 26%, and 5-year survival after R0 resection was 33%. No significant difference was detected between survival and tumor location, time period of treatment, or administration of adjuvant therapy. Analysis of various Western series reveals major differences between the cohorts under study, such as stage of disease, extent of resection, tumor type, and tumor location. Many of the reported differences among Western series may be due to cohort differences, such as stage of disease, extent of resection, tumor type, and tumor location.     

The effect of exercise intensity on the response to exercise rehabilitation in patients with intermittent claudication

PURPOSE: The purpose of this randomized trial was to compare the efficacy of a low-intensity exercise rehabilitation program vs a high-intensity program in changing physical function, peripheral circulation, and health-related quality of life in peripheral arterial disease (PAD) patients limited by intermittent claudication. METHODS: Thirty-one patients randomized to low-intensity exercise rehabilitation and 33 patients randomized to high-intensity exercise rehabilitation completed the study. The 6-month exercise rehabilitation programs consisted of intermittent treadmill walking to near maximal claudication pain 3 days per week at either 40% (low-intensity group) or 80% (high-intensity group) of maximal exercise capacity. Total work performed in the two training regimens was similar by having the patients in the low-intensity group exercise for a longer duration than patients in the high-intensity group. Measurements of physical function, peripheral circulation, and health-related quality of life were obtained on each patient before and after the rehabilitation programs. RESULTS: After the exercise rehabilitation programs, patients in the two groups had similar improvements in these measures. Initial claudication distance increased by 109% in the low-intensity group (P < .01) and by 109% in the high-intensity group (P < .01), and absolute claudication distance increased by 61% (P < 0.01) and 63% (P < .01) in the low-intensity and high-intensity groups, respectively. Furthermore, both exercise programs elicited improvements (P < .05) in peak oxygen uptake, ischemic window, and health-related quality of life. CONCLUSION: The efficacy of low-intensity exercise rehabilitation is similar to high-intensity rehabilitation in improving markers of functional independence in PAD patients limited by intermittent claudication, provided that a few additional minutes of walking is accomplished to elicit a similar volume of exercise.     

The Biomedical Research Hub: a federated platform for patient research data

ObjectiveThe objective was to develop and operate a cloud-based federated system for managing, analyzing, and sharing patient data for research purposes, while allowing each resource sharing patient data to operate their component based upon their own governance rules. The federated system is called the Biomedical Research Hub (BRH).Materials and MethodsThe BRH is a cloud-based federated system built over a core set of software services called framework services. BRH framework services include authentication and authorization, services for generating and assessing findable, accessible, interoperable, and reusable (FAIR) data, and services for importing and exporting bulk clinical data. The BRH includes data resources providing data operated by different entities and workspaces that can access and analyze data from one or more of the data resources in the BRH.ResultsThe BRH contains multiple data commons that in aggregate provide access to over 6 PB of research data from over 400 000 research participants.Discussion and conclusionWith the growing acceptance of using public cloud computing platforms for biomedical research, and the growing use of opaque persistent digital identifiers for datasets, data objects, and other entities, there is now a foundation for systems that federate data from multiple independently operated data resources that expose FAIR application programming interfaces, each using a separate data model. Applications can be built that access data from one or more of the data resources.