Aortic root dilation in acromegaly.

Previous studies have linked persistent elevations in growth hormone (GH) and insulin-like growth factor-1 (IGF-1) to cardiac abnormalities including aortic root dilation. Guidelines in the management of this dilation below the size recommended for surgery have not been well defined but follow-up and intervention when appropriate could be life-saving. We report the case of a man in his 60s who had been living with undiagnosed acromegaly for many years. His initial assessment through point-of-care ultrasound raised concerns about potential cardiac enlargement, prompting further investigation with a formal echocardiogram, which revealed a significant aortic root dilation measuring 4.5 cm. Subsequent blood tests confirmed elevated levels of IGF-1. Brain MRI showed a focal lesion in the pituitary gland, which was surgically resected, confirming the diagnosis of a GH-secreting pituitary adenoma. One year after surgery, a repeat CT angiogram of the chest demonstrated a stable size of the aortic root aneurysm.

Diagnostic dilemma: drug-induced vasculitis versus systemic vasculitis.

Drug-induced vasculitis can rarely cause inflammation and necrosis of blood vessel walls of both kidney and lung tissue. Diagnosis is challenging because of the lack of difference between systemic and drug-induced vasculitis in clinical presentation, immunological workup and pathological findings. Tissue biopsy guides diagnosis and treatment. Pathological findings must be correlated with clinical information to arrive at a presumed diagnosis of drug-induced vasculitis. We present a patient with hydralazine-induced antineutrophil cytoplasmic antibodies-positive vasculitis with a pulmonary-renal syndrome manifesting as pauci-immune glomerulonephritis and alveolar haemorrhage.

Spontaneous Retroperitoneal Hematoma in Vitamin C Deficiency.

Retroperitoneal hematoma is rare but potentially life-threatening. It is commonly caused by traumatic or iatrogenic vascular injury, retroperitoneal neoplasm, coagulopathy, chronic anticoagulation, or fibrinolytic therapy. However, retroperitoneal hematoma due to vitamin C deficiency is rare. Here, we report a case of 40 years old man who developed retroperitoneal hematoma in context of very low vitamin C. To our knowledge, this is the second described case of retroperitoneal hematoma from vitamin C deficiency.

Lamotrigine-associated hemophagocytic lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening disorder of excessive immune activation. It is mostly seen in the paediatric population and is rarely observed in adults. HLH can be inherited or acquired and is commonly triggered by activation of the immune system by an underlying viral infection or in immune system deficiency such as malignancy or underlying rheumatological disease. HLH is a difficult entity to diagnose due to the rarity of this disorder, variable clinical presentation and non-specific clinical and laboratory findings. HLH carries a high mortality if left untreated, and therefore prompt diagnosis and initiation of immunosuppressive, immunomodulatory and cytostatic medications are critical to improve survival in affected patients. Here, we present a case of lamotrigine-associated HLH. To our knowledge, only eight other cases of lamotrigine-associated HLH have been reported in adult patients.

A rare case of spontaneous tumor lysis syndrome in multiple myeloma.

Spontaneous tumor lysis syndrome is an uncommon oncologic emergency. It occurs when a massive number of malignant cells release their contents to the blood stream without previous cancer treatment. TLS carries a mortality rate exceeding 15%. Because of the high mortality rate, the key to the management of TLS continues to be early recognition of high-risk patients and using prophylactic measures to prevent its occurrence. However, it remains difficult to completely eradicate TLS, as a small proportion of patients with aggressive tumors develop spontaneous TLS prior to receiving any therapy. We present a case of 58-year-old male with recently diagnosed multiple myeloma. He was found to have hyperkalemia, hyperphosphatemia, hyperuricemia, hypocalcemia, elevated LDH levels, and acute renal failure, fulfilling the criteria of clinical TLS. He was treated with rasburicase, continuous renal replacement therapy, and dexamethasone.

A Resident Initiative Improves Hepatitis C Screening Rates in Primary Care Clinics.

BACKGROUND: Electronic reminders for clinical patient counseling have proven to be an effective response to national recommendations to increase risk factor and birth cohort hepatitis C virus (HCV) screening. It is not known whether a resident-led educational intervention alone could increase screening rates where support for electronic intervention may be limited. OBJECTIVE: We determined whether a resident-designed and resident-implemented educational intervention would significantly improve HCV screening rates in primary care clinics. METHODS: The baseline HCV screening rate was determined retrospectively in our resident community-based primary care clinics. We then implemented an educational intervention that included presenting during resident conference, posting signs in resident work areas, and providing educational pamphlets to patients. We collected screening rate data at 3 and 6 months postintervention. The screening rate was defined as patients screened in clinic divided by the number of patients eligible for screening. RESULTS: The screening rate increased significantly from preintervention (6%, 64 of 1023) to 3 months (35%, 363 of 1026) and 6 months (41%, 443 of 1070) and between 3 and 6 months (P < .001). The percentage of screened patients who pursued testing increased significantly between preintervention (62%, 16 of 26) and 6 months (81%, 105 of 130), and between 3 months (67%, 95 of 141) and 6 months (P = .019). CONCLUSIONS: An educational intervention designed and implemented by residents significantly increased the screening and testing rates for HCV in community-based resident clinics.

Toxicity mechanisms identification via gene set enrichment analysis of time-series toxicogenomics data: impact of time and concentration.

The advance in high-throughput "toxicogenomics" technologies, which allows for concurrent monitoring of cellular responses globally upon exposure to chemical toxicants, presents promises for next-generation toxicity assessment. It is recognized that cellular responses to toxicants have a highly dynamic nature, and exhibit both temporal complexity and dose-response shifts. Most current gene enrichment or pathway analysis lack the recognition of the inherent correlation within time series data, and may potentially miss important pathways or yield biased and inconsistent results that ignore dynamic patterns and time-sensitivity. In this study, we investigated the application of two score metrics for GSEA (gene set enrichment analysis) to rank the genes that consider the temporal gene expression profile. One applies a novel time series CPCA (common principal components analysis) to generate scores for genes based on their contributions to the common temporal variation among treatments for a given chemical at different concentrations. Another one employs an integrated altered gene expression quantifier-TELI (transcriptional effect level index) that integrates altered gene expression magnitude over the exposure time. By comparing the GSEA results using two different ranking metrics for examining the dynamic responses of reporter cells treated with various dose levels of three model toxicants, mitomycin C, hydrogen peroxide, and lead nitrate, the analysis identified and revealed different toxicity mechanisms of these chemicals that exhibit chemical-specific, as well as time-aware and dose-sensitive nature. The ability, advantages, and disadvantages of varying ranking metrics were discussed. These findings support the notion that toxicity bioassays should account for the cells' complex dynamic responses, thereby implying that both data acquisition and data analysis should look beyond simple traditional end point responses.

Stress signaling in response to polycyclic aromatic hydrocarbon exposure in Arabidopsis thaliana involves a nucleoside diphosphate kinase, NDPK-3.

MAIN CONCLUSION: The study is the first to reveal the proteomic response in plants to a single PAH stress, and indicates that NDPK3 is a positive regulator in the Arabidopsis response to phenanthrene stress. Polycyclic aromatic hydrocarbons (PAHs) are highly carcinogenic pollutants that are byproducts of carbon-based fuel combustion, and tend to persist in the environment for long periods of time. PAHs elicit complex, damaging responses in plants, and prior research at the physiological, biochemical, and transcriptional levels has indicated that reactive oxygen species (ROS) and oxidative stress play major roles in the PAH response. However, the proteomic response has remained largely unexplored. This study hypothesized that the proteomic response in Arabidopsis thaliana to phenanthrene, a model PAH, would include a strong oxidative stress signature, and would provide leads to potential signaling molecules involved. To explore that proteomic signature, we performed 2D-PAGE experiments and identified 30 proteins levels that were significantly altered including catalases (CAT), ascorbate peroxidase (APX), peroxiredoxins (POD), glutathione-S-transferase, and glutathione reductase. Also upregulated was nucleoside diphosphate kinase 3 (NDPK-3), a protein known to have metabolic and stress signaling functions. To address whether NDPK-3 functions upstream of the oxidative stress response, we measured levels of stress-responsive enzymes in NDPK-3 overexpressor, loss-of-function knockout, and wild-type plant lines. In the NDPK-3 overexpressor, the enzyme activities of APX, CAT, POD, as well as superoxide dismutase were all increased compared to wild type; in the NDPK-3 knockout line, these enzymes had reduced activity. This pattern occurred in untreated as well as phenanthrene-treated plants. These data support a model in which NDPK-3 is a positive regulator of the Arabidopsis stress response to PAHs.

Transcriptional responses to polycyclic aromatic hydrocarbon-induced stress in Arabidopsis thaliana reveal the involvement of hormone and defense signaling pathways.

BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) are toxic, widely-distributed, environmentally persistent, and carcinogenic byproducts of carbon-based fuel combustion. Previously, plant studies have shown that PAHs induce oxidative stress, reduce growth, and cause leaf deformation as well as tissue necrosis. To understand the transcriptional changes that occur during these processes, we performed microarray experiments on Arabidopsis thaliana L. under phenanthrene treatment, and compared the results to published Arabidopsis microarray data representing a variety of stress and hormone treatments. In addition, to probe hormonal aspects of PAH stress, we assayed transgenic ethylene-inducible reporter plants as well as ethylene pathway mutants under phenanthrene treatment. RESULTS: Microarray results revealed numerous perturbations in signaling and metabolic pathways that regulate reactive oxygen species (ROS) and responses related to pathogen defense. A number of glutathione S-transferases that may tag xenobiotics for transport to the vacuole were upregulated. Comparative microarray analyses indicated that the phenanthrene response was closely related to other ROS conditions, including pathogen defense conditions. The ethylene-inducible transgenic reporters were activated by phenanthrene. Mutant experiments showed that PAH inhibits growth through an ethylene-independent pathway, as PAH-treated ethylene-insensitive etr1-4 mutants exhibited a greater growth reduction than WT. Further, phenanthrene-treated, constitutive ethylene signaling mutants had longer roots than the untreated control plants, indicating that the PAH inhibits parts of the ethylene signaling pathway. CONCLUSIONS: This study identified major physiological systems that participate in the PAH-induced stress response in Arabidopsis. At the transcriptional level, the results identify specific gene targets that will be valuable in finding lead compounds and engineering increased tolerance. Collectively, the results open a number of new avenues for researching and improving plant resilience and PAH phytoremediation.

Decreased cerebrospinal fluid allopregnanolone levels in women with posttraumatic stress disorder.

BACKGROUND: Alterations in the gamma-amino-butyric acid (GABA) neurotransmitter system have been identified in some populations with posttraumatic stress disorder (PTSD). METHODS: To further investigate factors of relevance to GABAergic neurotransmission in PTSD, we measured cerebrospinal fluid (CSF) levels of allopregnanolone and pregnanolone combined (ALLO: congeners that potently and positively modulate effects of GABA at the GABA(A) receptor), 5alpha-dihydroprogesterone (5alpha-DHP: the immediate precursor for allopregnanolone), dehydroepiandrosterone (DHEA: a negative modulator of GABA(A) receptor function), and progesterone with gas chromatography, mass spectrometry in premenopausal women with (n = 9) and without (n = 10) PTSD. Subjects were free of psychotropic medications, alcohol, and illicit drugs; all were in the follicular phase of the menstrual cycle except three healthy and four PTSD subjects receiving oral contraceptives. RESULTS: There were no group differences in progesterone, 5alpha-DHP, or DHEA levels. The PTSD group ALLO levels were < 39% of healthy group levels. The ALLO/DHEA ratio correlated negatively with PTSD re-experiencing symptoms (n = -.82, p < 008; trend) and with Profile of Mood State depression/dejection scores (n = -0.70, p < 0008). CONCLUSION: Low CSF ALLO levels in premenopausal women with PTSD might contribute to an imbalance in inhibitory versus excitatory neurotransmission, resulting in increased PTSD re-experiencing and depressive symptoms.

Flexible titanium nailing for the treatment of the unstable pediatric tibial fracture.

Tibia fractures in the skeletally immature patient can usually be treated without surgery. The purpose of this study was to assess the use of flexible titanium nails in the tibia that requires operative stabilization. Over a 5-year period, 16 unstable tibia fractures in 14 patients were treated with flexible titanium intramedullary nails. All charts and radiographs were reviewed. The average age was 10 years 4 months. There were three open fractures. All fractures healed. Closed injuries obtained union by an average of 8 weeks, open fractures by an average of 15 weeks. There were no malunions. The average follow-up was 1 year 5 months. There were no instances of growth arrest, remanipulations, or refracture. In the unstable pediatric tibia fracture, flexible titanium nails are an effective treatment to obtain and maintain alignment and stability.