Down-regulation of OPA1 in patients with primary open angle glaucoma

PURPOSE: Heterozygous optic atrophy type1 (OPA1) mutations are responsible for dominant optic atrophy, and the down regulation of OPA1 expression in patients with Leber hereditary optic neuropathy may imply that Opa1 protein levels in mitochondria play a role in other spontaneous optic neuropathies as well. Mitochondrial and metabolic abnormalities may put the optic nerve at risk in primary open angle glaucoma (POAG), and this preliminary study was designed to investigate whether altered OPA1 expression might be present in the progressive optic neuropathy of POAG. METHODS: Patients were eligible for inclusion if they met standard clinical criteria for POAG, including age greater than 40 years, intraocular pressure ≥ 21 mmHg in at least one eye before treatment, normal-appearing anterior chamber angles bilaterally on gonioscopy, and optic nerve injury characteristic of POAG. RNA was extracted from leukocytes and converted to cDNA by reverse transcriptase enzyme, and real time PCR was used to assess expression levels of OPA1 and the β-globulin (HBB) housekeeping gene. The ratio of OPA1 expression to HBB expression (OPA1/HBB) for POAG patients was compared to that of controls and to clinical characteristics of POAG patients. RESULTS: Forty-three POAG patients and 27 controls were completely phenotyped with a full ophthalmologic examination and static perimetry. Mean age (POAG 67.9 years; controls 61.8 years) and sex (POAG 26 males/17 females; controls 11/16) were similar for the two groups. Mean OPA1/HBB of POAG patients (1.16, SD 0.26) was 18% lower than controls (1.41, SD 0.50), and this difference was statistically significant (p≤0.021). OPA1 expression differed between the groups (p≤0.037), but HBB expression did not differ (p≤0.24). OPA1/HBB was not correlated with any clinical feature of POAG patients. CONCLUSIONS: Transcriptional analysis of peripheral blood leucocytes is a limited model system for studying the consequences of mitochondrial abnormalities in the optic nerve. Nevertheless, OPA1 is known to affect mitochondrial stability and has now been implicated in several spontaneous optic neuropathies. Decreased OPA1 expression in POAG patients is another indication that mitochondrial function, and possibly mitochondrially-induced apoptosis, may play a role in the development of POAG

The fallacy of the BUN:creatinine ratio in critically ill patients

Abstract Background and objectives. Acute kidney injury (AKI) is common in critically ill patients and is associated with a high mortality rate. Pre-renal azotemia, suggested by a high blood urea nitrogen to serum creatinine (BUN:Cr) ratio (BCR), has traditionally been associated with a better prognosis than other forms of AKI. Whether this pertains to critically ill patients is unknown. Methods. We conducted a retrospective observational study of two cohorts of critically ill patients admitted to a single center: a derivation cohort, in which AKI was diagnosed, and a larger validation cohort. We analyzed associations between BCR and clinical outcomes: mortality and renal replacement therapy (RRT). Results. Patients in the derivation cohort (N ¼ 1010) with BCR >20 were older, predominantly female and white, and more severely ill. A BCR >20 was significantly associated with increased mortality and a lower likelihood of RRT in all patients, patients with AKI and patients at risk for AKI. Patients in the validation cohort (N ¼ 10 228) with a BCR >20 were older, predominantly female and white, and more severely ill. A BCR >20 was associated with increased mortality and a lower likelihood of RRT in all patients and in those at risk for AKI, BUN correlated with age and severity of illness. Conclusions. A BCR >20 is associated with increased mortality in critically ill patients. It is also associated with a lower likelihood of RRT, perhaps because of misinterpretation of the BCR. Clinicians should not use a BCR >20 to classify AKI in critically ill patients

The NT-ProBNP Test in Subjects with End-Stage Renal Disease on Hemodialysis Presenting with Acute Dyspnea: Is Knowing Worth the Cost?

Background. The NT-ProBNP/BNP test has been validated as a marker for determining the etiology of acute dyspnea. In the setting of end-stage renal disease on hemodialysis (ESRD on HD), the utility of the NT-ProBNP/BNP test has not been validated. This study examines the clinical utility of the NT-ProBNP test in the setting of ESRD on HD patients presenting with acute dyspnea. Methods. A retrospective case series of 250 subjects were admitted to Cooper University Hospital, 07/2010-03/2011, with ESRD and HD presenting with dyspnea. The incidences of echocardiography, cardiology consultation, and NT-ProBNP elevated and normal were examined. Correlation coefficients were calculated for NT-ProBNP with age (years), estimated dry weight (kg), amount of fluid removed (L), and ejection fraction (EF in %) among other echocardiography parameters. Results. Of the total sample 235 patients had NT-ProBNP levels performed. Cardiology consults were placed in 68.8% and 58% who underwent echocardiography. Of those for whom an echocardiography was performed estimated mean EFs of 54.6%, 50.8%, and 61.7% were observed among the NT-ProBNP elevated group, normal group, and no NT-ProBNP group, respectively. No differences were detected in all other echocardiography measurements. No correlation was observed between NT-ProBNP and age (), baseline EDW (), amount of fluid removed (), or EF (). Conclusion. In the setting of ESRD on HD, the NT-ProBNP test has no clinical utility in determining the etiology of acute dyspnea. This can be demonstrated through echocardiographic and therapeutic parameters measured in this study

Baseline peak systolic blood pressure/left ventricular end-systolic volume index (sBP/LVESVI) in survivors and non-survivors

Baseline sBP/LVESVI was not significantly different between survivors and non-survivors. Change in sBP/LVESVI from baseline at the point of maximum cardiac output response. A significantly greater mean increase in sBP/LVESVI was seen in survivors (p = 0.0188). Non-survivors had almost no mean change in this parameter with dobutamine infusion. Dash indicates mean values.<p><b>Copyright information:</b></p><p>Taken from "Cardiovascular response to dobutamine stress predicts outcome in severe sepsis and septic shock"</p><p>http://ccforum.com/content/12/2/R35</p><p>Critical Care 2008;12(2):R35-R35.</p><p>Published online 4 Mar 2008</p><p>PMCID:PMC2447556.</p><p></p

Psychosocial Outcomes

More than 65 million Americans care for family members with chronic illness; most are middle-aged women who are employed. 1 Family caregivers provide almost 75% of caregiving support in the United States and receive little or no help from family members or healthcare professionals. Unpaid care provided by informal family caregivers is estimated in value at more than $450 billion a year, which is more than was spent on Medicaid in 2009. The burdens placed on informal caregivers include the physical, emotional, social, and financial costs related to caring for a loved one, all of which can affect quality of life (QOL). 4-8 Physical demands of caregiving include time spent in hands-on care of the recipient and transportation to medical appointments. Other examples of the physical demands of caregiving include lifting, bathing, and ambulating that can result in caregiver exhaustion, weakness, or tiredness. Family caregivers may suffer from lack of appetite and changes in sleep patterns related to disruptions in their sleep-wake cycle. 9-11 The emotional effects of providing care for people with chronic illness include feelings of sadness, depression, loneliness, and lack of hope

Baseline left ventricular ejection fraction in survivors and non-survivors

Seven of fourteen non-survivors and five of eight survivors had a reduced ejection fraction (less than 55 per cent). The lower mean ejection fraction in survivors did not reach statistical significance in comparison to the higher ejection fraction in non-survivors. Change in left ventricular ejection fraction from baseline at the point of maximum cardiac index response. The mean increase in left ventricular ejection fraction was significantly greater in survivors than in non-survivors (p = 0.0160). Dash indicates mean values.<p><b>Copyright information:</b></p><p>Taken from "Cardiovascular response to dobutamine stress predicts outcome in severe sepsis and septic shock"</p><p>http://ccforum.com/content/12/2/R35</p><p>Critical Care 2008;12(2):R35-R35.</p><p>Published online 4 Mar 2008</p><p>PMCID:PMC2447556.</p><p></p