ICAM1 depletion reduces spinal metastasis formation in vivo and improves neurological outcome

INTRODUCTION Clinical treatment of spinal metastasis is gaining in complexity while the underlying biology remains unknown. Insufficient biological understanding is due to a lack of suitable experimental animal models. Intercellular adhesion molecule-1 (ICAM1) has been implicated in metastasis formation. Its role in spinal metastasis remains unclear. It was the aim to generate a reliable spinal metastasis model in mice and to investigate metastasis formation under ICAM1 depletion. MATERIAL AND METHODS B16 melanoma cells were infected with a lentivirus containing firefly luciferase (B16-luc). Stable cell clones (B16-luc) were injected retrogradely into the distal aortic arch. Spinal metastasis formation was monitored using in vivo bioluminescence imaging/MRI. Neurological deficits were monitored daily. In vivo selected, metastasized tumor cells were isolated (mB16-luc) and reinjected intraarterially. mB16-luc cells were injected intraarterially in ICAM1 KO mice. Metastasis distribution was analyzed using organ-specific fluorescence analysis. RESULTS Intraarterial injection of B16-luc and metastatic mB16-luc reliably induced spinal metastasis formation with neurological deficits (B16-luc:26.5, mB16-luc:21 days, p<0.05). In vivo selection increased the metastatic aggressiveness and led to a bone specific homing phenotype. Thus, mB16-luc cells demonstrated higher number (B16-luc: 1.2±0.447, mB16-luc:3.2±1.643) and increased total metastasis volume (B16-luc:2.87±2.453 mm3, mB16-luc:11.19±3.898 mm3, p<0.05) in the spine. ICAM1 depletion leads to a significantly reduced number of spinal metastasis (mB16-luc:1.2±0.84) with improved neurological outcome (29 days). General metastatic burden was significantly reduced under ICAM1 depletion (control: 3.47×10(7)±1.66×10(7); ICAM-1-/-: 5.20×10(4)±4.44×10(4), p<0.05 vs. control) CONCLUSION Applying a reliable animal model for spinal metastasis, ICAM1 depletion reduces spinal metastasis formation due to an organ-unspecific reduction of metastasis development.

Nitric oxide inhalation reduces brain damage, prevents mortality, and improves neurological outcome after subarachnoid hemorrhage by resolving early pial microvasospasms.

Subarachnoid hemorrhage is a stroke subtype with particularly bad outcome. Recent findings suggest that constrictions of pial arterioles occurring early after hemorrhage may be responsible for cerebral ischemia and - subsequently - unfavorable outcome after subarachnoid hemorrhage. Since we recently hypothesized that the lack of nitric oxide may cause post-hemorrhagic microvasospasms, our aim was to investigate whether inhaled nitric oxide, a treatment paradigm selectively delivering nitric oxide to ischemic microvessels, is able to dilate post-hemorrhagic microvasospasms; thereby improving outcome after experimental subarachnoid hemorrhage. C57BL/6 mice were subjected to experimental SAH. Three hours after subarachnoid hemorrhage pial artery spasms were quantified by intravital microscopy, then mice received inhaled nitric oxide or vehicle. For induction of large artery spasms mice received an intracisternal injection of autologous blood. Inhaled nitric oxide significantly reduced number and severity of subarachnoid hemorrhage-induced post-hemorrhage microvasospasms while only having limited effect on large artery spasms. This resulted in less brain-edema-formation, less hippocampal neuronal loss, lack of mortality, and significantly improved neurological outcome after subarachnoid hemorrhage. This suggests that spasms of pial arterioles play a major role for the outcome after subarachnoid hemorrhage and that lack of nitric oxide is an important mechanism of post-hemorrhagic microvascular dysfunction. Reversing microvascular dysfunction by inhaled nitric oxide might be a promising treatment strategy for subarachnoid hemorrhage.

Erratum to: Vascular endothelial growth factor induces contralesional corticobulbar plasticity and functional neurological recovery in the ischemic brain.

Erratum to: Acta Neuropathol (2012) 123:273–284. DOI 10.1007/s00401‑011‑0914‑z. The authors would like to correct Fig. 3 of the original manuscript, since the image in Fig. 3b does not correspond to a VEGF treated animal. Corrected Fig. 3 is shown below. We apologize for this mistake.

When to Monitor CD4 Cell Count and HIV RNA to Reduce Mortality and AIDS-Defining Illness in Virologically Suppressed HIV-Positive Persons on Antiretroviral Therapy in High-Income Countries: A Prospective Observational Study.

OBJECTIVE To illustrate an approach to compare CD4 cell count and HIV-RNA monitoring strategies in HIV-positive individuals on antiretroviral therapy (ART). DESIGN Prospective studies of HIV-positive individuals in Europe and the USA in the HIV-CAUSAL Collaboration and The Center for AIDS Research Network of Integrated Clinical Systems. METHODS Antiretroviral-naive individuals who initiated ART and became virologically suppressed within 12 months were followed from the date of suppression. We compared 3 CD4 cell count and HIV-RNA monitoring strategies: once every (1) 3 ± 1 months, (2) 6 ± 1 months, and (3) 9-12 ± 1 months. We used inverse-probability weighted models to compare these strategies with respect to clinical, immunologic, and virologic outcomes. RESULTS In 39,029 eligible individuals, there were 265 deaths and 690 AIDS-defining illnesses or deaths. Compared with the 3-month strategy, the mortality hazard ratios (95% CIs) were 0.86 (0.42 to 1.78) for the 6 months and 0.82 (0.46 to 1.47) for the 9-12 month strategy. The respective 18-month risk ratios (95% CIs) of virologic failure (RNA >200) were 0.74 (0.46 to 1.19) and 2.35 (1.56 to 3.54) and 18-month mean CD4 differences (95% CIs) were -5.3 (-18.6 to 7.9) and -31.7 (-52.0 to -11.3). The estimates for the 2-year risk of AIDS-defining illness or death were similar across strategies. CONCLUSIONS Our findings suggest that monitoring frequency of virologically suppressed individuals can be decreased from every 3 months to every 6, 9, or 12 months with respect to clinical outcomes. Because effects of different monitoring strategies could take years to materialize, longer follow-up is needed to fully evaluate this question.

The illness experiences of patients and their family members living with congestive heart failure

Purpose. To investigate and understand the illness experiences of patients and their family members living with congestive heart failure (CHF). ^ Design. Focused ethnographic design. ^ Setting. One outpatient cardiology clinic, two outpatient heart failure clinics, and informants' homes in a large metropolitan city located in southeast Texas. ^ Sample. A purposeful sampling technique was used to select a sample of 28 informants. The following somewhat overlapping, sampling strategies were used to implement the purposeful method: criterion; typical case; operational construct; maximum variation; atypical case; opportunistic; and confirming and disconfirming case sampling. ^ Methods. Naturalistic inquiry consisted of data collected from observations, participant observations, and interviews. Open-ended semi-structured illness narrative interviews included questions designed to elicit informant's explanatory models of the illness, which served as a synthesizing framework for the analysis. A thematic analysis process was conducted through domain analysis and construction of data into themes and sub-themes. Credibility was enhanced through informant verification and a process of peer debriefing. ^ Findings. Thematic analysis revealed that patients and their family members living with CHF experience a process of disruption, incoherence, and reconciling. Reconciling emerged as the salient experience described by informants. Sub-themes of reconciling that emerged from the analysis included: struggling; participating in partnerships; finding purpose and meaning in the illness experience; and surrendering. ^ Conclusions. Understanding the experiences described in this study allows for a better understanding of living with CHF in everyday life. Findings from this study suggest that the experience of living with CHF entails more than the medical story can tell. It is important for nurses and other providers to understand the experiences of this population in order to develop appropriate treatment plans in a successful practitioner-patient partnership. ^

Trapped in the Bell Jar: Mental Illness in College Students

This is a magazine article that explores the rising problem of mental health in college students, focusing on Connecticut. It explores the experiences of three college students dealing with depression and bipolar disorder, a family who lost a child to suicide, and the measures taken by colleges in Connecticut to curb the problem.

The illness narratives of Hispanic American women with coronary heart disease (CHD): An ethnographic approach

Purpose. To provide a descriptive representation of the illness narratives described by Hispanic American women with CHD. ^ Design. Focused ethnographic design. ^ Setting. One outpatient general medicine clinic, one nurse-managed health promotion clinic, and informants' homes in a large metropolitan city located in southeast Texas. ^ Sample. Purposeful sampling from two different sites resulted in 17 interviews being conducted with 14 informants. ^ Method. Focused ethnographic techniques were employed in the designation of participants for the study, data collection, analysis and re-presentation. Audiotaped interviews and fieldwork were transcribed verbatim and analyzed through an iterative process of data reduction, data display, drawing conclusions and verification. ^ Findings. The developing conceptual framework that emerged from the data is labeled after the overarching experience described by informants, the experience of Embodied Exhaustion. Embodied Exhaustion, as described in this study, refers to an ongoing, dynamic, indeterminate experience of mind-body exhaustion resulting from a complex constellation of biologic, psychological and social distresses occurring over the life course. The experience consists of three categories: Taking Care of Others, Wearing Down and Hurting Hearts. Two stabilizing forces were identified: Collective Self and Believing in God. ^ Conclusions. The findings of this study emphasize the importance of framing all research, theory and practice targeting Hispanic women with CHD within a sociocentric paradigm. Nursing is challenged to provide care that extends beyond the physical body of the patient to include the social context of illness, especially the family. ^

DNA incisions stimulate genetic instability of triplet repeat sequences related to human hereditary neurological diseases

The molecular mechanisms responsible for the expansion and deletion of trinucleotide repeat sequences (TRS) are the focus of our studies. Several hereditary neurological diseases including Huntington's disease, myotonic dystrophy, and fragile X syndrome are associated with the instability of TRS. Using the well defined and controllable model system of Escherichia coli, the influences of three types of DNA incisions on genetic instability of CTG•CAG repeats were studied: DNA double-strand breaks (DSB), single-strand nicks, and single-strand gaps. The DNA incisions were generated in pUC19 derivatives by in vitro cleavage with restriction endonucleases. The cleaved DNA was then transformed into E. coli parental and mutant strains. Double-strand breaks induced deletions throughout the TRS region in an orientation dependent manner relative to the origin of replication. The extent of instability was enhanced by the repeat length and sequence (CTG•CAG vs. CGG•CCG). Mutations in recA and recBC increased deletions, mutations in recF stabilized the TRS, whereas mutations in ruvA had no effect. DSB were repaired by intramolecular recombination, versus an intermolecular gene conversion or crossover mechanism. 30 nt gaps formed a distinct 30 nt deletion product, whereas single strand nicks and gaps of 15 nts did not induce expansions or deletions. Formation of this deletion product required the CTG•CAG repeats to be present in the single-stranded region and was stimulated by E. coli DNA ligase, but was not dependent upon the RecFOR pathway. Models are presented to explain the DSB induced instabilities and formation of the 30 nucleotide deletion product. In addition to the in vitro creation of DSBs, several attempts to generate this incision in vivo with the use of EcoR I restriction modification systems were conducted. ^

Physician coding for mental illness reimbursement and the need for mental health parity

Many patients with anxiety and depression initially seek treatment from their primary care physicians. Changes in insurance coverage and current mental parity laws, make reimbursement for services a problem. This has led to a coding dilemma for physicians seeking payment for their services. This study seeks to determine first the frequency at which primary care physicians use alternative coding, and secondly, if physicians would change their coding practices, provided reimbursement was assured through changes in mental parity laws. A mail survey was sent to 260 randomly selected primary care physicians, who are family practice, internal medicine, and general practice physicians, and members of the Harris County Medical Society. The survey evaluated the physicians' demographics, the number of patients with psychiatric disorders seen by primary care physicians, the frequency with which physicians used alternative coding, and if mental parity laws changed, the rate at which physicians would use a psychiatric illness diagnosis as the primary diagnostic code. The overall response rate was 23%. Only 47 of the 59 physicians, who responded, qualified for the study and of those 45% used a psychiatric disorder to diagnose patients with a primary psychiatric disorder, 47% used a somatic/symptom disorder, and 8% used a medical diagnosis. From the physicians who would not use a psychiatric diagnosis as a primary ICD-9 code, 88% were afraid of not being reimbursed and 12% were worried about stigma or jeopardizing insurability. If payment were assured using a psychiatric diagnostic code, 81% physicians would use a psychiatric diagnosis as the primary diagnostic code. However, 19% would use an alternative diagnostic code in fear of stigmatizing and/or jeopardizing patients' insurability. Although the sample size of the study design was adequate, our survey did not have an ideal response rate, and no significant correlation was observed. However, it is evident that reimbursement for mental illness continues to be a problem for primary care physicians. The reformation of mental parity laws is necessary to ensure that patients receive mental health services and that primary care physicians are reimbursed. Despite the possibility of improved mental parity legislation, some physicians are still hesitant to assign patients with a mental illness diagnosis, due to the associated stigma, which still plays a role in today's society. ^

The illness experience of persons with Parkinson's Disease

Background. Parkinson's disease is a chronic, progressive, age-related, neurodegenerative disorder with no known cause or promising cure. While substantial information is known about the pathophysiology of Parkinson's disease, little is known about the illness experience of persons living with the disease. The purpose of this study was to understand how persons with Parkinson's disease construct their illness experience and manage living with their illness on a daily basis. ^ Method. A qualitative study with an ethnographic approach employed the strategies of participant observations and fieldwork. Field data were generated from a two year exposure to two Parkinson's disease support groups in east Texas. Open-ended semi-structured interviews with seven men and seven women with Parkinson's disease were also conducted. These data were combined and analyzed using thematic analysis. ^ Findings. The illness experience is described through the metaphor "Sailing the Sea in The Eye of the Storm." This metaphor served as the overarching theme that covered the two interacting content themes of the voyage of Daily Negotiations in the Midst of Uncertainty and Reconstruction of the Self with Parkinson's Disease. Daily negotiations incorporated navigating daily activities with the uncertainty of both the progression and daily vicissitudes of the disease. Participants described their symptoms as progressive imprisonment that interfered with daily activities. The progressive nature of the disease required the participants to reconstruct their perceptions of themselves. Reconstructing the self involved the paradoxical balancing of preserving the self while simultaneously releasing aspects of the former self to reconstruct the self with Parkinson's disease. This process was reflected in four exemplars: I Know Me." "It's Still Me," "See Me." and "Remember Me." ^ Conclusions. This qualitative study illuminated the struggle of persons in dealing with the uncertainties and fluctuations of Parkinson's disease and the process of reconstructing their perceptions of themselves. The meaning and reconstruction of the illness experience expressed by participants will inform understanding beyond the disease itself to the illness experience that these participants must deal with on a daily basis. ^

Theory of uncertainty in illness in patients with cancer of unknown primary origin: Structure providers as antecedents of uncertainty in a population of cancer patients with an unknown primary diagnosis

Uncertainty has been found to be a major component of the cancer experience and can dramatically affect psychosocial adaptation and outcomes of a patient's disease state (McCormick, 2002). Patients with a diagnosis of Carcinoma of Unknown Primary (CUP) may experience higher levels of uncertainty due to the unpredictability of current and future symptoms, limited treatment options and an undetermined life expectancy. To date, only one study has touched upon uncertainty and its' effects on those with CUP but no information exists concerning the effects of uncertainty regarding diagnosis and treatment on the distress level and psychosocial adjustment of this population (Parker & Lenzi, 2003). ^ Mishel's Uncertainty in Illness Theory (1984) proposes that uncertainty is preceded by three variables, one of which being Structure Providers. Structure Providers include credible authority, the degree of trust and confidence the patient has with their doctor, education and social support. It was the goal of this study to examine the relationship between uncertainty and Structure Providers to support the following hypotheses: (1) There will be a negative association between credible authority and uncertainty, (2) There will be a negative association between education level and uncertainty, and (3) There will be a negative association between social support and uncertainty. ^ This cross-sectional analysis utilized data from 219 patients following their initial consultation with their oncologist. Data included the Mishel Uncertainty in Illness Scale (MUIS) which was used to determine patients' uncertainty levels, the Medical Outcomes Study-Social Support Scale (MOSS-SSS) to assess patients, levels of social support, the Patient Satisfaction Questionnaire (PSQ-18) and the Cancer Diagnostic Interview Scale (CDIS) to measure credible authority and general demographic information to assess age, education, marital status and ethnicity. ^ In this study we found that uncertainty levels were generally higher in this sample as compared to other types of cancer populations. And while our results seemed to support most of our hypothesis, we were only able to show significant associations between two. The analyses indicated that credible authority measured by both the CDIS and the PSQ was a significant predictor of uncertainty as was social support measured by the MOSS-SS. Education has shown to have an inconsistent pattern of effect in relation to uncertainty and in the current study there was not enough data to significantly support our hypothesis. ^ The results of this study generally support Mishel's Theory of Uncertainty in Illness and highlight the importance of taking into consideration patients, psychosocial factors as well as employing proper communication practices between physicians and their patients.^

Comparing experience of diabetes care with chronic illness care in the primary care clinic using the Patient Assessment of Chronic Illness Care (PACIC)

Purpose. The overall purpose of the study was to evaluate the patient experience relevant to the Chronic Care Model as measured by the PACIC. Chronic illness care of patients with diabetes was compared to those with other chronic illnesses. In addition, chronic illness care of Hispanics was compared to those of other race/ethnicity. ^ Methods. The setting of this study was 20 primary care practices located in San Antonio, TX. The subjects in this study were consecutive adult patients age >18 yrs. Data was collected via a survey (PACIC) administered to 40-60 consecutive adult patients in each primary care clinic who presented for a scheduled appointment. ^ Results. Patient experience of the Chronic Care Model is different among those with diabetes than those with other chronic diseases: those with diabetes report a higher PACIC score. (P = 0.012) Although Hispanic patients report a higher PACIC score, patient experience of the Chronic Care Model among Hispanic patients is not significantly different than that of patients of other race/ethnicity regardless of chronic disease. (P = 0.053) After controlling for the patient characteristics of age, education, health status, and race/ethnicity, the diabetes status of the patient remains significantly associated with the outcome, the PACIC score. (P = 0.033) ^ Conclusions. Diabetes is associated with a greater experience of the Chronic Care model. Contributing factors to diabetes patients’ greater experience of the Chronic Care Model include the greater heath care use and higher self-care needs unique to individuals with diabetes. Special consideration must be given to the specific needs diabetic patients to ensure effective interventions, higher patient education, greater patient compliance, and lower health care costs. ^

Foodborne illness - An age old problem requiring contemporary solutions

Foodborne illness has always been with us, and food safety is an increasingly important public health issue affecting populations worldwide. In the United States of America, foodborne illness strikes millions of people and kills thousands annually, costing our economy billions of dollars in medical care expense and lost productivity. The nature of food and foodborne illness has changed dramatically in the last century. The regulatory systems have evolved to better assure a safe food supply. The food production industry has invested heavily to meet regulatory requirement and to improve the safety of their products. Educational efforts have increased public awareness of safe food handling practices, empowering consumers to fulfill their food safety role. Despite the advances made, none of the Healthy People 2010 targets for reduction of foodborne pathogens has been reached. There is no single solution to eliminating pathogen contamination from all classes of food products. However, irradiation seems especially suited for certain higher-risk foods such as meat and poultry and its use should advance the goal of reducing foodborne illness by minimizing the presence of pathogenic organisms in the food supply. This technology has been studied extensively for over 50 years. The Food and Drug Administration has determined that food irradiation is safe for use as approved by the Agency. It is time to take action to educate consumers about the benefits of food irradiation. Consumer demand will compel industry to meet demand by investing in facilities and processes to assure a consistent supply of irradiated food products. ^

Foodborne illness, food inspection policy and restaurants in the U.S.

Objectives. The purpose of this paper is to conduct a literature review of research relating to foodborne illness, food inspection policy, and restaurants in the United States. Aim 1: To convey the public health importance of studying restaurant food inspection policies and suggest that more research is needed in this field, Aim 2: To conduct a systematic literature review of recent literature pertaining to this subject such that future researchers can understand the: (1) Public perception and expectations of restaurant food inspection policies; (2) Arguments in favor of a grade card policy; and, conversely; (3) Reasons why inspection policies may not work. ^ Data/methods. This paper utilizes a systematic review format to review articles relating to food inspections and restaurants in the U.S. Eight articles were reviewed. ^ Results. The resulting data from the literature provides no conclusive answer as to how, when, and in what method inspection policies should be carried out. The authors do, however, put forward varying solutions as to how to fix the problem of foodborne illness outbreaks in restaurants. These solutions include the implementation of grade cards in restaurants and, conversely, a complete overhaul of the inspection policy system.^ Discussion. The literature on foodborne disease, food inspection policy, and restaurants in the U.S. is limited and varied. But, from the research that is available, we can see that two schools of thought exist. The first of these calls for the implementation of a grade card system, while the second proposes a reassessment and possible overhaul of the food inspection policy system. It is still unclear which of these methods would best slow the increase in foodborne disease transmission in the U.S.^ Conclusion. In order to arrive at solutions to the problem of foodborne disease transmission as it relates to restaurants in this country, we may need to look at literature from other countries and, subsequently, begin incremental changes in the way inspection policies are developed and enforced.^

The effects of obesity in critical illness

Obesity continues to cripple the United States in terms of increasing health care expenditures and its rising rate of prevalence in epidemic proportions. The comorbidities associated with obesity have continued to represent some of the most deadly chronic health diseases. The most vulnerable subpopulation, the critically ill, suffers from not only the comorbid conditions but also the complications encountered within their specialized care. Taking into account the rising prevalence rates of obesity and critical care patients, it has come to the attention of many researchers to measure the trends associated with these two health conditions. Hospital mortality was found to be lower in higher BMI groups whereas there was no difference between BMI groups for ICU mortality. Length of stay and mechanical ventilation were both higher for obese rather than non-obese patients. The most prevalent disease states among the obese critically injured was cardiovascular and pulmonary disease. In conclusion, obesity is not independently associated with increased ICU mortality, but the comorbidities linked to obesity prove a greater threat to vitality.^