Myelopathy after zoster virus infection in immunocompetent patients: A case series

ContextAfter primary infection, varicella zoster virus (VZV) becomes latent in ganglionic neurons. If immunity declines, VZV is reactivated and can spread to the dermatome depending from this ganglion and in some cases to the spinal cord. Myelopathy is rare and may develop in the absence of skin rash making the diagnosis very difficult.FindingsFrom 1994 to 2014, we collected five observations of clinically and laboratory confirmed zoster myelopathy. The age of our patients ranged from 14 to 78. They did not have any significant past medical history. Four patients had a history of radicular rash. After 3 weeks (4–45 days), patients presented paraparesis, sensory loss, and sphincter dysfunction. Cerebrospinal fluid (CSF) analysis revealed an elevated protein level (5/5cases) and pleocytosis (2/5 cases). Spinal cord magnetic resonance imaging (MRI) demonstrated T2 hyper intense lesions with swelling and contrast enhancement. The diagnosis was supported by laboratory evidence, including the detection of VZV antibodies in the CSF. All patients received intravenous acyclovir and two patients received IV methylprednisolone. A marked improvement was observed in most of the patients within 2 months.Conclusion /Clinical RelevanceBased on our patients and on previous reports, we highlight the possibility of the occurrence of VZV myelopathy in immunocompetent subjects. The diagnosis must be evoked even in the absence of typical skin lesions. In this case, spinal cord MRI and virological tests are useful tools for the diagnosis. We also emphasize on the importance of accurate diagnosis to enable the specific treatment and ameliorate the outcome.     

Prevalence of elevated blood pressure in 563,704 adult patients with stroke presenting to the ED in the United States

PURPOSE: The aim of this study was to estimate the prevalence of elevated blood pressure in adult patients with acute stroke in the United States (US). METHODS: Patients with stroke were classified by initial systolic blood pressure (SBP) into 4 categories using demographic, clinical, and treatment data from the National Hospital Ambulatory Medical Care Survey, the largest study of use and provision of emergency department (ED) services in the United States. We also compared the age-, sex-, and ethnicity-adjusted rates of elevated blood pressure strata, comparable with stages 1 and 2 hypertension in the US population. RESULTS: Of the 563704 patients with stroke evaluated, initial SBP was below 140 mm Hg in 173120 patients (31%), 140 to 184 mm Hg in 315207 (56%), 185 to 219 mm Hg in 74586 (13%), and 220 mm Hg or higher in 791 (0.1%). The mean time interval between presentation and evaluation was 40 +/- 55, 33 +/- 39, 25 +/- 27, and 5 +/- 1 minutes for increasing SBP strata (P = .009). A 3- and 8-fold higher rate of elevated blood pressure strata was observed in acute stroke than the existing rates of stages 1 and 2 hypertension in the US population. Labetalol and hydralazine were used in 6126 (1%) and 2262 (0.4%) patients, respectively. Thrombolytics were used in 1283 patients (0.4%), but only in those with SBP of 140 to 184 mm Hg. CONCLUSIONS: In a nationally representative large data set, elevated blood pressure was observed in over 60% of the patients presenting with stroke to the ED. Elevated blood pressure was associated with an earlier evaluation; however, the use of thrombolytics was restricted to patients with ischemic stroke with SBP below 185 mm Hg.     

Autoimmune hepatitis as an adverse effect of long-term methotrexate therapy

Methotrexate (MTX) is one of the most commonly used medicines in the treatment of psoriatic arthritis. The drug can produce steatosis and cirrhosis. Autoimmune hepatitis is a rare and serious adverse effect. We describe the case of a 53-year-old woman who developed autoimmune hepatitis after a long-term use of MTX for psoriatic arthritis. Hepatitis was completely resolved 4 months after stopping this drug. The pathophysiologic mechanisms of a drug-induced autoimmunity are unclear and complex. This report confirms the need to monitor liver enzymes carefully in patients using long-term treatment with MTX for psoriasis or rheumatoid arthritis.KEY WORDS: Autoimmune hepatitis, drug-induced autoimmunity, methotrexate, psoriatic arthritis     

Biological significance of promoter hypermethylation of p14/ARF gene: Relationships to p53 mutational status in Tunisian population with colorectal carcinoma

One of the most important pathways which are frequently affected in colorectal cancer is p53/ (MDM2)/p14ARF pathway. We aim to determine the methylation pattern of p14/ARF in relation to mutation of p53. This correlation was studied to investigate whether their alterations could be considered as a predictor factor of prognosis in colorectal cancer and whether it can be useful in early-stage diagnosis. Statistical analyses show that p14/ARF hypermethylation was correlated with rectum location (p?=?0.004), primary TNM stage (p?=?0.016), and advanced Astler–Coller stage (p?=?0.024). The RT-PCR that revel 31 % of patients did not express p14/ARF mRNA or at very low level. A high concordance between CpG hypermethylation and the low levels (p?<?0.005) was shown. In addition, our analyses demonstrate that patients with mutation in the p53 gene have a lack of the protein expression (p?<?0.005). This category with negative expression of p53 had a shorter survival rate (p?<?0.005). On the one hand, MSP pattern of p14/ARF were correlated with a lack of p53 expression (p?=?0.007). We found that p53/p14ARF pathway was frequently deregulated among our patients. In our study, we demonstrate that hypermethylation of p14/ARF occurs early during CRC tumorogenesis. However, we did not find correlation between p14/ARF and survival. These results suggest that p14/ARF methylation pattern may constitute a predictor factor of CRC in early stage but it could not be considered as a prognostic factor. On the other hand and because of the reversibility of the methylation mechanism, it may be appropriate to target the demethylation of p14/ARF to develop new drogues for CRC.     

Hammada scoparia flavonoids and rutin kill adherent and chemoresistant leukemic cells

In search for compounds able to reduce cell adhesion-mediated drug resistance (CAM-DR), we studied effects of Hammada scoparia extracts on leukemic cells adherent or in suspension. We show that H. scoparia flavonoidic fraction and its compound rutin induce apoptosis specifically in adherent leukemic cells and abolish CAM-DR. Importantly, rutin inhibited survival of adherent leukemic progenitors (CD34⁺38⁻123⁺) but spared normal progenitors (CD34⁺38⁻). The pro-apoptotic effects of rutin were correlated with a decrease of active GSK3β and inhibitors of GSK3β reproduced rutin-induced cytotoxicity. This study uncovers the potential of H. scoparia flavonoids and rutin to overcome CAM-DR in acute myeloid leukemia.     

Effect of purified Russell’s viper venom-factor X activator (RVV-X) on renal hemodynamics, renal functions, and coagulopathy in rats

Acute renal failure (ARF) is the most frequent and a serious complication in victims of Russell’s viper snakebites. Russell’s viper venom-factor X activator (RVV-X) has been identified as a main procoagulant enzyme involving coagulopathy, which might be responsible for changes in renal hemodynamics and renal functions. Here, we purified RVV-X from crude Russell’s viper venom to study renal hemodynamics, renal functions, intravascular clot, and histopathological changes in Sprague-Dawley rats. Changes in renal hemodynamics and renal functions were evaluated by measuring the mean arterial pressure, glomerular filtration rate (GFR), effective renal plasma flow (ERPF), effective renal blood flow (ERBF), renal vascular resistance (RVR), and fractional excretion of electrolytes. After 10 min, rats receiving both crude venom and purified RVV-X decreased GFR, ERPF, and ERBF and increased RVR. These changes correlated to renal lesions. Along with the determination of intravascular clot, rats injected with purified RVV-X increased the average D-dimer level and reached a peak at 10 min, declined temporarily, and then reached another peak at 30 min. The temporal association between clots and renal dysfunction was observed in rats within 10 min after the injection of purified RVV-X. These findings suggested RVV-X as a major cause of renal failure through intravascular clotting in the renal microcirculation.