N -Ethyl- N -Nitrosourea Induces Retinal Photoreceptor Damage in Adult Rats

Seven-week-old male Lewis rats received a single intraperitoneal injection of N-ethyl-N-nitrosourea (ENU) (100, 200, 400 or 600 mg/kg), and retinal damage was evaluated 7 days after the treatment. Sequential morphological features of the retina and retinal DNA damage, as determined by a TUNEL assay and phospho-histone H2A.X (γ-H2AX), were analyzed 3, 6, 12, 24 and 72 hr, 7 days, and/or 30 days after 400 mg/kg ENU treatment. Activation of the nuclear enzyme poly (ADP-ribose) polymerase (PARP) was analyzed immunohistochemically by poly (ADP-ribose) (PAR) expression in response to DNA damage of the retina. All rats that received ≥ 400 mg/kg of ENU developed retinal degeneration characterized by the loss of photoreceptor cells in both the central and peripheral retina within 7 days. In the 400 mg/kg ENU-treated rats, TUNEL-positive signals were only located in the photoreceptor cells and peaked 24 hr after ENU treatment. The γ-H2AX signals in inner retinal cells appeared at 24 hr and peaked at 72 hr after ENU treatment, and the PAR signals selectively located in the photoreceptor cell nuclei appeared at 12 hr and peaked at 24 hr after ENU treatment. However, degeneration was restricted to photoreceptor cells, and no degenerative changes in inner retinal cells were seen at any time points. Retinal thickness and the photoreceptor cell ratio in the central and peripheral retina were significantly decreased, and the retinal damage ratio was significantly increased 7 days after ENU treatment. In conclusion, ENU induced retinal degeneration in adult rats that was characterized by photoreceptor cell apoptosis through PARP activity

Autonomic function in gastroparesis and chronic unexplained nausea and vomiting: Relationship with etiology, gastric emptying, and symptom severity

BackgroundAutonomic dysfunction can be present in patients with idiopathic and diabetic gastroparesis. The role of autonomic dysfunction relating to gastric emptying and upper gastrointestinal symptoms in patients with gastroparesis and chronic unexplained nausea and vomiting (CUNV) remains unclear. The aim of our study is to evaluate autonomic function in patients with gastroparesis and CUNV with respect to etiology, gastric emptying and symptom severity.MethodsWe studied 242 patients with chronic gastroparetic symptoms recruited at eight centers. All patients had a gastric emptying scintigraphy within 6 months of the study. Symptom severity was assessed using the gastroparesis cardinal symptom index. Autonomic function testing was performed at baseline enrollment using the ANX 3.0 autonomic monitoring system which measures heart rate variability and respiratory activity measurements.Key ResultsLow sympathetic response to challenge (Valsalva or standing) was the most common abnormality seen impacting 89% diabetic and 74% idiopathic patients. Diabetics compared to idiopathics, exhibited greater global hypofunction with sympathetic (OR = 4.7, 95% CI 2.2‐10.3; P < .001) and parasympathetic (OR = 7.2, 95% CI 3.4‐15.0; P < .001) dysfunction. Patients with delayed gastric emptying were more likely to have paradoxic parasympathetic excessive during sympathetic challenge [(Valsalva or standing) 40% vs. 26%, P = .05]. Patients with more severe symptoms exhibited greater parasympathetic dysfunction compared to those with mild‐moderate symptoms: resting sympathovagal balance [LFa/RFa 1.8 (1.0‐3.1) vs. 1.2 (0.6‐2.3), P = .006)] and standing parasympathetic activity [0.4 (0.1‐0.8) vs. 0.6 (0.2‐1.7); P = .03].ConclusionsAutonomic dysfunction was common in patients with gastroparesis and CUNV. Parasympathetic dysfunction was associated with delayed gastric emptying and more severe upper gastrointestinal symptoms. Conversely, sympathetic hypofunction was associated with milder symptoms.InferencesGastroparesis and CUNV may be a manifestation of GI autonomic dysfunction or imbalance, such that sympathetic dysfunction occurs early on in the manifestation of chronic upper GI symptoms, while parasympathetic dysfunction results in more severe symptoms and delayed gastric emptying.Sympathetic withdrawal (low sympathetic activity in response to a sympathetic challenge) was the most common autonomic abnormality found among all patients.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156243/2/nmo13810_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156243/1/nmo13810.pd

Biological impact of geometric uncertainties: what margin is needed for intra-hepatic tumors?

<p>Abstract</p> <p>Background</p> <p>To evaluate and compare the biological impact on different proposed margin recipes for the same geometric uncertainties for intra-hepatic tumors with different tumor cell types or clinical stages.</p> <p>Method</p> <p>Three different margin recipes based on tumor motion were applied to sixteen IMRT plans with a total of twenty two intra-hepatic tumors. One recipe used the full amplitude of motion measured from patients to generate margins. A second used 70% of the full amplitude of motion, while the third had no margin for motion. The biological effects of geometric uncertainty in these three situations were evaluated with Equivalent Uniform Doses (EUD) for various survival fractions at 2 Gy (SF₂).</p> <p>Results</p> <p>There was no significant difference in the biological impact between the full motion margin and the 70% motion margin. Also, there was no significant difference between different tumor cell types. When the margin for motion was eliminated, the difference of the biological impact was significant among different cell types due to geometric uncertainties. Elimination of the motion margin requires dose escalation to compensate for the biological dose reduction due to the geometric misses during treatment.</p> <p>Conclusions</p> <p>Both patient-based margins of full motion and of 70% motion are sufficient to prevent serious dosimetric error. Clinical implementation of margin reduction should consider the tumor sensitivity to radiation.</p

Essentials in Accident and Emergency Medicine Radiation Injury: Response and Treatment

The discovery of radiation has enabled great healthcare advances as well as catastrophic injury. This paper reviews major historical incidents of public radiation exposure and the evolution of standards affecting today’s public and health care workers. Current patient care and response assessment to radiation exposure are reviewed. The strengths of modern radiation therapy and the need for continuous process improvements to ensure optimal patient care and secure safe environments are identified. The discovery of radiation has brought significant scientific achievements as well as catastrophic injury

The Sun Health Research Institute Brain Donation Program: Description and Eexperience, 1987–2007

The Brain Donation Program at Sun Health Research Institute has been in continual operation since 1987, with over 1000 brains banked. The population studied primarily resides in the retirement communities of northwest metropolitan Phoenix, Arizona. The Institute is affiliated with Sun Health, a nonprofit community-owned and operated health care provider. Subjects are enrolled prospectively to allow standardized clinical assessments during life. Funding comes primarily from competitive grants. The Program has made short postmortem brain retrieval a priority, with a 2.75-h median postmortem interval for the entire collection. This maximizes the utility of the resource for molecular studies; frozen tissue from approximately 82% of all cases is suitable for RNA studies. Studies performed in-house have shown that, even with very short postmortem intervals, increasing delays in brain retrieval adversely affect RNA integrity and that cerebrospinal fluid pH increases with postmortem interval but does not predict tissue viability

Plasma Dynamics

Contains reports on four research projects.National Science Foundation (Grant ECS82-13485)University of Maryland (Subcontract A200728)U.S. Air Force - Office of Scientific Research (Grant AFOSR-84-0026B)U.S. Department of Energy (Contract DE-ACO2-78-ET-51013)National Science Foundation (Grant ECS82-13430

Radiation Injury and Emergency Medicine

The discovery of radiation has led to many advances. Guidelines have been created to minimize radiation exposure and treatment management following both unintentional and intentional exposure. The effects of radiation exposure on specific tissues varies. Tragic consequences can result, ranging from severe, acute injury to long- lasting effects that present years after the initial exposure. In this chapter we provide observations that demonstrate the importance of understanding guidelines to minimize radioactive exposure and the expectations and treatment management following exposure. For the safety and well-being of patients, health care professionals need to remain well-informed to minimize the risks of this tool

Clinical Relevance and Discriminatory Value of Elevated Liver Aminotransferase Levels for Dengue Severity

Dengue is a global public health problem, as the incidence of the disease has reached hyperendemic proportions in recent decades. Infection with dengue can cause acute, febrile illness or severe disease, which can lead to plasma leakage, bleeding, and organ impairment. One of the most prominent clinical characteristics of dengue patients is increased aspartate and alanine aminotransferase liver enzyme levels. The significance of this is uncertain, as it is transient in the majority of cases, and most patients recover uneventfully without liver damage. In this study, we characterized this phenomenon in the context of dengue severity and found that, although liver enzyme levels increased concurrently with dengue severity, they could not sufficiently discriminate between dengue fever and dengue hemorrhagic fever or between non-severe and severe dengue. Therefore clinicians may need to use other parameters to distinguish dengue severity in patients during early illness

Plasma Dynamics

Contains reports on five research projects.U.S. Air Force - Office of Scientifc Research (Contract AFOSR 84-0026)National Science Foundation (Grant ECS 85-14517)Lawrence Livermore National Laboratory (Subcontract 6264005)National Science Foundation (Grant ECS 85-15032)U.S. Department of Energy (Contract DE-ACO2-78-ET-51013)U.S. Department of Energy (Contract DE-ACO2-ET-51013

Perceptions of Community HIV/STI Risk Among U.S Women Living in Areas with High Poverty and HIV Prevalence Rates

Although studies have consistently demonstrated that women at high risk for HIV and non-HIV sexually transmitted infections (STIs) tend to underestimate their individual risk, little is known about how women at risk perceive their community’s HIV/STI risk. We explored perceptions of community HIV/ STI risk among U.S. women living in areas with high poverty and HIV prevalence rates as part of a qualitative substudy of the Women’s HIV SeroIncidence Study. Semi-structured focus groups were conducted. Data were coded and analyzed using the constant comparative method. Participants expressed the perception that their communities were at elevated HIV/STI risk, mostly due to contextual and structural factors such as lack of access to health care and education. Findings suggest that HIV prevention messages that target U.S. women at high risk for HIV may be strengthened by addressing the high perceived community HIV/ STI risk driven by structural factors