Citations

ABSTRACTIntroductionThe clinical significance of striational antibodies (StrAbs) detected in the course of paraneoplastic antibody testing is unknown.MethodsWe compared all 203 striational antibody (StrAb)‐seropositive patients identified (2004–2005) during evaluation for paraneoplastic antibodies with age‐ and sex‐matched seronegative controls.ResultsThymoma and myasthenia gravis (MG) were significantly more common among cases (P<0.0001). Cancers more rarely detected after StrAb detection were adenocarcinoma in 5 patients and sarcoma in 3 patients. All patients who had a cancer identified after StrAb testing had a titer of ≥1:7680 or a coexisting muscle AChR‐binding antibody. Autoimmune disorders more commonly observed among cases (with any StrAb value) included: hypothyroidism; rheumatoid arthritis; and pernicious anemia (all P<0.05).ConclusionsStrAbs may serve as a diagnostic clue for an autoimmune diagnosis. There is a low likelihood of oncological significance in patients with StrAb titers <1:7680 without coexisting paraneoplastic Abs. Muscle Nerve, 2013

Renal artery stenosis (RAS) is an important cause of chronic renal dysfunction. Recent studies have underscored a critical role for CCL2 (MCP-1)-mediated inflammation in the progression of chronic renal damage in RAS and other chronic renal diseases. In vitro studies have implicated p38 MAPK as a critical intermediate for the production of CCL2. However, a potential role of p38 signaling in the development and progression of chronic renal disease in RAS has not been previously defined. We sought to test the hypothesis that inhibition of p38 MAPK ameliorates chronic renal injury in mice with RAS. We established a murine RAS model by placing a cuff on the right renal artery and treated mice with the p38 inhibitor SB203580 or vehicle for 2 wk. In mice treated with vehicle, the cuffed kidney developed interstitial fibrosis, tubular atrophy, and interstitial inflammation. In mice treated with SB203580, the RAS-induced renal atrophy was reduced (70% vs. 39%, P < 0.05). SB203580 also reduced interstitial inflammation and extracellular matrix deposition but had no effect on the development of hypertension. SB203580 partially blocked the induction of CCL2, CCL7 (MCP-3), CC chemokine receptor 2 (CCR2), and collagen 4 mRNA expression in the cuffed kidneys. In vitro, blockade of p38 hindered both TNF-α and TGF-β-induced CCL2 upregulation. Based on these observations, we conclude that p38 MAPK plays a critical role in the induction of CCL2/CCL7/CCR2 system and the development of interstitial inflammation in RAS.

Introduction: Collaborative care management (CCM) for the treatment of depression has been shown to be an effective therapy. CCM can be seen as a resource intensive treatment. Early identification of patients who would not be effectively treated with CCM could allow for alteration of therapy or change in modality. Methods: A retrospective case-controlled study used 132 patients with prolonged enrollment (>1 year) in CCM (cases) and 396 randomized CCM patients who achieved remission within 6 months (controls). The hypothesis was that by studying the epidemiology of patients in prolonged care management (PCM), characteristics could be determined to help define this group. Results: With regression modeling, the odds of a patient having PCM at 1 year was highly significant for those unmarried patients (odds ratio [OR] = 1.736, confidence interval [CI] = 1.115-2.703, P = .015) with dysthymia (OR = 2.362, CI = 1.104-5.052, P = .027) and severe depression (OR = 2.856, CI = 1.551-5.260, P = .001). The adjusted baseline Patient Health Questionnaire–9 (PHQ-9) score showed a difference of 16.0 for the cases versus 14.8 for the controls ( P < .001). By 10 weeks, the difference is much larger at (10.7 vs 4.9, P < .001). At 26 weeks, the control group had an adjusted average PHQ-9 score of 2.0, whereas the case group was still elevated at 10.2 ( P < .001). Conclusions: Case-controlled analysis of PCM patients demonstrated independent predictors (such as unmarried status, diagnosis of dysthymia or severe depression), however, no baseline data was of sufficient clarity to suggest changes in clinical practice. The trend of the patient’s PHQ-9 over time was strongly suggestive of allowing differentiation between the groups.

BackgroundPrevalence and risk factors for focal hemosiderin deposits are important considerations when planning amyloid‐modifying trials for treatment and prevention of Alzheimer's disease (AD).MethodsSubjects were cognitively normal (n = 171), early‐mild cognitive impairment (MCI) (n = 240), late‐MCI (n = 111), and AD (n = 40) from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Microhemorrhages and superficial siderosis were assessed at baseline and on all available MRIs at 3, 6, and 12 months. β‐amyloid load was assessed with 18F‐florbetapir positron emission tomography.ResultsPrevalence of superficial siderosis was 1% and prevalence of microhemorrhages was 25% increasing with age (P < .001) and β‐amyloid load (P < .001). Topographic densities of microhemorrhages were highest in the occipital lobes and lowest in the deep/infratentorial regions. A greater number of microhemorrhages at baseline was associated with a greater annualized rate of additional microhemorrhages by last follow‐up (rank correlation = 0.49; P < .001).ConclusionsFocal hemosiderin deposits are relatively common in the ADNI cohort and are associated with β‐amyloid load.

Traumatic brain injury (TBI) is a global public health epidemic. In the US alone, more than 3 million people sustain a TBI annually. It is one of the most disabling injuries as it may cause motor and sensory deficits and lead to severe cognitive, emotional, and psychosocial impairment, crippling vital areas of higher functioning. Fueled by the recognition of TBI as the “signature injury” in our wounded soldiers in Iraq and Afghanistan, and its often devastating impact on athletes playing contact sports, interest in TBI and TBI research has increased dramatically. Unfortunately, despite increased awareness of its detrimental consequences, there has been little progress in developing effective TBI interventions. Recent evidence, however, strongly indicates that nutritional intervention may provide a unique opportunity to enhance the neuronal repair process after TBI. To date, two omega-3 fatty acids, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), have the most promising laboratory evidence for their neuro-restorative capacities in TBI. Although both animal models and human studies of brain injuries suggest they may provide benefits, there has been no clinical trial evaluating the effects of n-3 fatty acids on resilience to, or treatment, of TBI. This article reviews the known functions of n-3 fatty acids in the brain and their specific role in the cellular and biochemical pathways underlying neurotraumatic injury. We also highlight recent studies on the therapeutic impact of enhanced omega 3 intake in vivo , and how this may be a particularly promising approach to improving functional outcome in patients with TBI.

Abstract Effective treatment with antidepressants is currently limited by factors that affect treatment compliance, including delay in onset of therapeutic effects and intolerable side-effects. Recent data suggest that use of antidepressant combinations with different mechanisms of action may be a better first-line strategy prior to augmentation with other drug classes. The rationale for this approach is that combining multiple pharmacological actions affecting multiple monoamine targets produces greater efficacy. Several new multi-modal compounds are in development and early results for the most advanced agents indicate shorter onset of therapeutic effects and improved tolerability. By modulating multiple receptors and transmitter systems, it is hoped that these new agents may also treat some of the associated symptoms of major depressive disorder, such as anxiety and cognitive dysfunction.

AbstractBackgroundFunctional GI syndromes are known to be very prevalent, but this may be linked to unrecognized medications use. We aimed to estimate the prevalence of PPI, antidepressant, and narcotic use in the general population, and to evaluate the association between each medication and functional GI syndromes adjusting for potential confounders.MethodsIn 2008 and 2009, newly revised versions of a validated bowel disease questionnaire were mailed to a community‐based cohort (total mailed = 8006) of Olmsted County, MN residents; 3831 returned the questionnaire (response rate = 48.0%). Medication usage, specifically PPIs, narcotics, and antidepressants in the last year, was elicited via three separate questions on the questionnaire. The association between each medication and GI symptom complexes was assessed using multiple variable logistic regression models.Key ResultsA total of 3515 of the respondents (92%) had complete data (mean age: 61 ± 15; 54% female). The overall proportion reporting PPI use was 20% (95% CI: 19, 22), narcotic use 12% (95% CI: 11, 13), and antidepressant use 15% (95% CI: 14, 16). PPI use was significantly associated with IBS status (OR = 1.4, 95% CI 1.1, 1.7) as well as with GERD (OR = 3.5, 95% CI 2.7, 4.4) and dyspepsia (OR = 2.0, 95% CI 1.5, 2.7). The association of PPI use with IBS was not explained by coexistent GERD or dyspepsia. Antidepressant use was significantly associated only with bloating (OR = 1.6, 1.1, 2.2).Conclusions & InferencesSome medications that may alter intestinal transit or bowel flora are commonly utilized by the general population, and PPI use appears to be linked to IBS.

OBJECTIVE: To describe a case of torsades de pointes (TdP) in a patient treated with aripiprazole. CASE SUMMARY: A 42-year-old white male with schizophrenia, diabetes, hypertension, and a history of stroke was admitted to the intensive care unit following 2 days of fever, diarrhea, and altered mental status. Following the resolution of his acute illness, previous therapy with quetiapine 400 mg orally at bedtime was resumed for schizophrenia and presumed delirium. Quetiapine was discontinued after 1 dose because of QTc interval prolongation. Twenty-three days later, with a baseline Q Tc interval of 414 milliseconds, aripiprazole 2.5 mg orally once daily was initiated. Following 5 days of aripiprazole therapy, the patient had a cardiac arrest due to TdP. Normal sinus rhythm was restored after 30 seconds of cardiopulmonary resuscitation, 1 shock of 200 Joules, and 4 g of intravenous magnesium sulfate. Serial electrocardiographs obtained after aripiprazole discontinuation revealed resolution of QTc interval prolongation. DISCUSSION: Aripiprazole is a second-generation antipsychotic that may be selected for patients with prolonged QTc intervals and at risk for TdP. Data from trials indicate that aripiprazole has minimal effects on the QTc interval. However, in this case, aripiprazole was associated with TdP in a patient with minimal risk factors. The Naranjo probability scale was used to determine a probable association between aripiprazole and the development of TdP. To our knowledge, this is the first reported case of TdP associated with the use of aripiprazole. CONCLUSIONS: Five days of low-dose aripiprazole therapy was associated with the development of TdP in a man with minimal risk factors. Clinicians should be aware of this potential adverse drug event with aripiprazole.