Case Reports of Fatalities Involving Tianeptine in the United States.

Tianeptine is a tricyclic anti-depressant that is also known to have opioid receptor activity. We present two fatal cases of tianeptine intoxication in Texas in which tianeptine was used recreationally. The first case involved a 28-year-old white male found alone on the floor of his locked residence. He had a history of drug abuse but no other toxicological findings. The second case involved a 30-year-old white male found on the floor of the bathroom in his home. Drug paraphernalia and bags labeled as tianeptine powder were found at both scenes. In response to the first case, our laboratory developed a method for quantitation of tianeptine by LC-MS-MS. This method was then validated according to SWGTOX guidelines for specificity, calibration model, limit of detection, limit of quantitation, accuracy, precision, ion suppression, and carryover. This method was successfully used to determine tianeptine concentrations in postmortem blood in two cases. In these cases, tianeptine was measured at 2.0 mg/L and 8.4 mg/L. These represent the first known tianeptine fatalities in Texas and in the United States.

Higher sensitivity of capillary electrophoresis in detecting hemoglobin A2'compared to traditional gel electrophoresis.

HbA2' (also called Hb B2) is the most common delta-globin chain defect and is reported to occur in 1-2% of the African American population. The major clinical significance of HbA2' is that the failure to detect it might lead to an underestimation of the total HbA2, leading to failure to diagnose ß-thalassemia minor. In order to diagnose ß-thalassemia minor, both HbA2 and HbA2' levels must be combined.Hb A2' accounts for a small percentage (1-2%) of the total hemoglobin in heterozygotes. It is difficult to detect this small amount by traditional gel electrophoresis. Using HPLC Hb A2' is easily detected as it produces a minor peak in the S window. Other conditions which might interfere with detection of HbA2' by HPLC include Hb S trait or Hb SS disease (Hb A2' hidden in the S peak), transfused Hb SS (Hb S peak may be very small), Hb C trait or Hb CC disease (glycosylated Hb C elutes in the S window), and Hb G (Hb G2 elutes in the S window). All of the above conditions, including Hb A2', occur most commonly in the same ethnic group (African American). We reviewed 654 consecutive cases over a period of three months for the presence of Hb A2' in our laboratory where capillary electrophoresis is used as the primary diagnostic tool. We detected seven cases (1.07 %) of HbA2'. In contrast, we did not detect any HbA2' using conventional gel electrophoresis in the last one year (2,580 cases). Although in none of the seven cases the sum of Hb A2 and Hb A2' exceeded 3.5%, we believe that capillary electrophoresis allows for a better detection of Hb A2' than gel electrophoresis and HPLC.

High false-positive rate for monoclonal gammopathy using capillary electrophoresis (CAPILLARYS 2) alone.

BACKGROUND: Capillary zone electrophoresis (CZE) is a newer method of performing serum protein electrophoresis and is considered to be faster and more efficient than agarose gel method. We decided to evaluate CZE as an efficient screening tool for monoclonal gammopathies, and we began recommending immunofixation studies in cases with such minor/subtle distortions to avoid missing monoclonal gammopathies. METHODS: We evaluated 163 serum protein agarose gel electrophoresis (SPAGE) samples between October and November 2011, and 447 serum protein CZE (SPCZE) samples between January 2012 to February 2012 and August 2012 to September 2012. RESULTS: Immunofixation studies were recommended in 51 of 163 cases (31.3%) performed by SPAGE, and in 274 of 447 cases (61.3%) performed by SPCZE. While using SPAGE, of the 51 cases recommended for immunofixation (24 were performed to date), six cases (25.0%) were positive for monoclonal gammopathy. In contrast, while using SPCZE, of the 274 cases recommended for immunofixation (118 were performed to date), 18 cases (15.2%) were positive for monoclonal gammopathy. Using the SPCZE method, of these 18 cases, five (27.8%) had minor/subtle distortions without obvious peaks. Our recommendation rate for immunofixation studies has thus almost doubled (61.3% vs. 31.3%) with the adoption of SPCZE. Yet, using SPCZE has not translated to detecting more cases of true monoclonal gammopathies. CONCLUSION: Therefore, we conclude that there is a high false-positive rate for monoclonal gammopathy using CE alone.

Cutaneous phaeohyphomycosis caused by Paraconiothyrium cyclothyrioides.

Paraconiothyrium cyclothyrioides is a recently described coelomycetous fungal species. We present a case in a renal transplant patient with chronic skin lesions of the lower extremities caused by P. cyclothyrioides. Treatment with posaconazole led to complete resolution of the lesions. P. cyclothyrioides should be considered an opportunistic human pathogen in immunocompromised patients.

Novel FDG-PET findings in anti-NMDA receptor encephalitis: a case based report.

The clinical manifestation and nuclear imaging findings in a 15-year-old boy with anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis are described in this case report. The previously healthy patient presented with new onset hallucinations, seizure, and within a week, his mental status rapidly deteriorated to nonverbal with oro-lingual-facial dyskinesias. An extensive laboratory work-up for encephalopathy was negative. Repeated brain magnetic resonance imaging (MRI) studies were normal. On day 26 of admission, nuclear imaging using fluorodeoxyglucose positron emission tomography (FDG-PET) showed global hypometobolism with a prominent focally intense hypermetabolic lesion in the right cerebellar cortex. Diagnosis of anti-NMDAR encephalitis was confirmed with quantitative serology. The patient showed clinical signs of improvement after 2 courses of intravenous immunoglobulin therapy over 4 weeks. On day 46, repeat brain FDG-PET showed overall improvement but in contrast to the previous, the right cerebellar cortex showed focal hypometabolism. This is the first reported case of such findings using FDG-PET in anti-NMDAR encephalitis.

Quantitative mapping of ion channel regulation by visual cycle activity in rodent photoreceptors in vivo.

PURPOSE: To test the hypothesis that the extent of outer retina uptake of manganese, measured noninvasively with manganese-enhanced MRI (MEMRI), is a quantitative biomarker of photoreceptor ion channel regulation by visual cycle activity. METHODS: Four groups of animals were studied: control rats adapted to three different background light intensities, dark-adapted control mice systemically pretreated with retinylamine, and dark-adapted mice with a nonsense mutation in exon 3 of the RPE65 gene (RPE65(rd12)) with and without systemic 11-cis-retinal pretreatment. In all cases, rodents were anesthetized and studied with MEMRI 4 hours after manganese administration IP. Central retinal thickness and intraretinal ion channel regulation were measured from the MEMRI data. RESULT: No differences (P>0.05) in retinal thickness were noted within any arm of this study. In rats, manganese uptake was inversely proportional to the background light intensity in the outer retina but not in the inner retina. Specific inhibition at the level of RPE65 activity, either acutely with retinylamine or chronically in RPE65(rd12) mice, similarly reduced (P<0.05) outer retinal manganese uptake compared with that in control mice. In RPE65(rd12) mice, outer retinal manganese uptake returned to normal (P>0.05) after 11-cis retinal treatment. Inner retinal uptake was supernormal (P<0.05) in retinylamine-treated mice but normal in untreated or 11-cis treated RPE65(rd12) mice. CONCLUSIONS: The present data support measuring the extent of manganese uptake in the outer retina as an analytic noninvasive metric of visual cycle regulation of photoreceptor ion channel activity in vivo.

Melatonin as a principal component of red light therapy.

Melatonin is well recognized for its role as a potent antioxidant and is directly implicated in the free radical theory of aging [1] [Reiter RJ, Pablos MI, Agapito TT, Guerrero JM. Melatonin in the context of the free radical theory of aging. Ann N Y Acad Sci 1996;786:362-78]. Moreover, melatonin has been shown to retard age-related increases in lipid peroxidation and oxidative damage [2] [Okatani Y, Wakatsuki A, Reiter RJ. Melatonin protects hepatic mitochondrial respiratory chain activity in senescence-accelerated mice. J Pineal Res 2002;32:143-8] and to act directly upon the immune system [3] [Poon AM, Liu ZM, Pang CS, Brown GM, Pang SF. Evidence for a direct action of melatonin on the immune system. Biol Signals 1994;3:107-17]. This report focuses on characterizing documented functions of melatonin in the context of red light therapy and proposes that melatonin is a potential mediator of red light's therapeutic effects, a hypothesis that is as yet untested. Red light therapy (670 nm, 4J/cm(2)) has been shown to restore glutathione redox balance upon toxicological insult and enhance both cytochrome c oxidase and energy production, all of which may be affected by melatonin. The red light treatment has also been successfully implemented in the clinical setting for its effectiveness in reducing both the number of incidences and severity of oral mucositis resulting in part from the chemotherapy and/or radiation administered prior to bone marrow transplants. Moreover, red light therapy improves wound healing and is being further tested for its ability to ameliorate toxicant-induced retinal and visual cortical neuron damage. Researchers in the growing field of light therapy may be in a position to draw from and collaborate with melatonin researchers to better characterize this alternative treatment.