Comparison of Pain With Ultrasound-Guided Intra-Articular Hip Injections With and Without Prior Subcutaneous Local Anesthesia.

OBJECTIVE: To compare pain levels of intra-articular hip steroid injections performed with and without prior subcutaneous local anesthesia (LA) injection. DESIGN: Randomized prospective study. SETTING: University-based musculoskeletal clinic. PARTICIPANTS: Forty-one adult patients undergoing a first-time ultrasound-guided unilateral intra-articular hip steroid injection. INTERVENTIONS: Subjects were randomized into 1 of 2 groups: intra-articular hip injection with prior subcutaneous LA with 2 mL of lidocaine 1% (With LA) or hip injection without prior subcutaneous LA (Without LA). Visual analog scale (VAS) pain scores (0-100) were collected before and after each injection. MAIN OUTCOME MEASURES: Visual analog scale pain score for the intra-articular hip injection. RESULTS: Of the 41 total subjects, 18 were randomized to the Without LA group and 23 to the With LA group. There was no significant difference in baseline (preprocedure) VAS scores between the Without LA (mean ± SD = 39.2 ± 27.2) and With LA (41.2 ± 24.0) groups (P = 0.864). The mean ± SD VAS score for the subcutaneous LA injection in the With LA group was 20.4 ± 16.1. There was no significant difference in VAS scores for the intra-articular hip injection between the Without LA (48.5 ± 27.7) and With LA (39.5 ± 25.7) groups (P = 0.232). CONCLUSIONS: Subcutaneous injection of lidocaine before an intra-articular hip injection did not significantly decrease pain from the intra-articular hip injection. Providers may perform intra-articular hip injections with a 22-gauge 3.5-inch spinal needle without the need for an extra subcutaneous LA injection.

Rapid nitrogen loss from ectomycorrhizal pine germinants signaled by their fungal symbiont.

Ectomycorrhizal fungi supply their plant partners with nitrogen but can also retain substantial amounts. The concentration of nitrogen in the soil and the amount of carbon supplied from the host seem to influence the proportion of N retained by the fungus. In an experiment designed to determine whether differential supply of nitrogen to two plants influenced nitrogen transfer from fungus to plant within a mycorrhizal network, we observed rapid, substantial loss of nitrogen from pine seedlings. The loss occurred when the mycorrhizal fungus experienced a sudden increase in nitrogen supply. We grew Pinus contorta seedlings in association with Suillus tomentosus in low-nitrogen microcosms where some nitrogen was accessible only by hyphae. After 70 days, foliage of some seedlings was treated with nitrogen. Three days later, hyphal nutrient media were replaced with water or a solution containing nitrogen. Foliar treatment did not affect nitrogen transfer by the fungus to shoots, but by day 75, seedling nitrogen contents had dropped by 60% in microcosms where nitrogen had been added to the hyphal compartments. Those seedlings retained only 55% of the nitrogen originally present in the seed. Loss of nitrogen did not occur if water was added or the hyphae were severed. Because of the severing effect, we concluded that S. tomentosus triggered the loss of seedling nitrogen. Nitrogen may have been lost through increased root exudation or transfer to the fungus. Access to nitrogen from nutrient-rich germinants would benefit rhizosphere microorganisms, including ectomycorrhizal fungi colonizing pine from spores after wildfire.

High-Dimensional Analysis of Postsplenectomy Peripheral Immune Cell Changes.

Although the consequences of splenectomy are well understood in mice, much less is known about the immunologic changes that occur following splenectomy in humans. We sought to characterize the circulating immune cell populations of patients before and after elective splenectomy to determine if these changes are related to postsplenectomy survival outcomes. Retrospective clinical information was collected from 95 patients undergoing elective splenectomy compared with 91 patients undergoing pancreaticoduodenectomy (Whipple procedure). We further analyzed peripheral blood from five patients in the splenectomy group, collected before and after surgery, using single-cell cytometry by time-of-flight mass spectrometry. We compared pre- and postsplenectomy data to characterize both the major and minor immune cell populations in significantly greater detail. Compared with patients undergoing a Whipple procedure, splenectomized patients had significant and long-lasting elevated counts of lymphocytes, monocytes, and basophils. Cytometry by time-of-flight mass spectroscopy analysis demonstrated that the elevated lymphocytes primarily consisted of naive CD4+ T cells and a population of activated CD25+CD56+CD4+ T cells, whereas the elevated monocyte counts were mainly mature, activated monocytes. We also observed a significant increase in the expression of the chemokine receptors CCR6 and CCR4 on several cellular populations. Taken together, these data indicate that significant immunological changes take place following splenectomy. Whereas other groups have compared splenectomized patients to healthy controls, this study compared patients undergoing elective splenectomy to those undergoing a similar major abdominal surgery. Overall, we found that splenectomy results in significant long-lasting changes in circulating immune cell populations and function.

11-Ketotestosterone Is the Dominant Circulating Bioactive Androgen During Normal and Premature Adrenarche.

Context: Adrenarche refers to the rise of dehydroepiandrosterone sulfate (DHEA-S) associated with the development of a functional adrenal zona reticularis. Clinical features of adrenarche include onset of body odor, axillary hair, and pubic hair, which reflect increased androgen action. An early rise in adrenal androgens, or premature adrenarche (PremA), is a risk factor for adverse metabolic profiles in adolescence and adulthood. The bioactive androgens associated with adrenarche and PremA remain poorly understood. The adrenal gland is a potential source of testosterone (T) and the 11-oxygenated derivatives 11ß-hydroxytestosterone (11OHT) and 11-ketotestosterone (11KT). Objective: The objective of this study was to characterize the adrenal androgen biome contributing to adrenarche and PremA. Participants and Methods: With the use of mass spectrometry, 19 steroids including the 11-oxygenated derivatives of T were measured in sera obtained from girls with PremA (n = 37; 4 to 7 years) and age-matched girls (n = 83; 4 to 10 years). Results: In reference population girls, dehydroepiandrosterone, DHEA-S, androstenediol-3-sulfate, T, and 11KT all increased at the onset of adrenarche (6 to 8 years) and beyond (9 to 10 years) (P < 0.05 vs younger subjects 4 to 5 years). T, 11OHT, and 11KT were further elevated in PremA vs age-matched girls (P < 0.001). Circulating concentrations of 11KT during adrenarche and PremA exceeded those of T and 11OHT (11KT > T ≥ 11OHT). Androgen receptor activity and nuclear translocation studies demonstrated that 11KT is a potent androgen similar to T. Conclusions: Our findings suggest that 11KT is the dominant bioactive androgen in children during adrenarche and PremA. Its androgenic capacity suggests that it may be responsible for the phenotypic changes seen in these phenomena.

Age-dependent Increases in Adrenal Cytochrome b5 and Serum 5-Androstenediol-3-sulfate.

CONTEXT: Adrenal production of dehydroepiandrosterone sulfate (DHEA-S) increases throughout childhood owing to expansion of the zona reticularis (ZR). ZR features cells with a steroidogenic phenotype distinct from that of the adjacent zona fasciculata, with higher expression of cytochrome b5 type A (CYB5A) and steroid sulfotransferase type 2A1 but decreased 3ß-hydroxysteroid dehydrogenase type 2 (HSD3B2). In addition to DHEA-S, three adrenal Δ5-steroid sulfates could provide additional tools to define adrenal maturation. OBJECTIVE: This study sought to simultaneously measure serum levels of four adrenal Δ5-steroid sulfates, pregnenolone sulfate (Preg-S), 17α-hydroxypregnenolone sulfate (17OHPreg-S), DHEA-S, and 5-androstenediol-3-sulfate (Adiol-S) as a function of age and relate their production to the age-dependent adrenal localization of CYB5A. PARTICIPANTS AND METHODS: Δ5-steroid sulfates were quantified by liquid chromatography-tandem mass spectrometry in sera from 247 normal children (129 males,118 females) age 1.5-18 y and 42 adults (20 males, 22 females). Immunofluorescence localized HSD3B2 and CYB5A in normal adrenal glands from subjects age 2-35 y. Finally, HAC15 adrenocortical cells were transduced with lentiviral short hairpin RNA to suppress CYB5A expression. RESULTS: Of the Δ5-steroid sulfates quantified, DHEA-S was most abundant. Adiol-S increased in parallel with DHEA-S. Steroid ratios (17OHPreg-S/DHEA-S) suggested increases in 17,20-lyase activity during childhood. Immunofluorescence analysis showed age-related increases in ZR CYB5A immunoreactivity. Furthermore, silencing CYB5A in HAC15 adrenocortical cells significantly reduced DHEA-S and Adiol-S production. CONCLUSION: Adiol-S shows a similar age-related increase to that of DHEA-S. This likely results from the childhood expansion of CYB5A-expressing ZR, which enhances 17,20-lyase activity and the production of DHEA-S and Adiol-S.

Unraveling the role of dark septate endophyte (DSE) colonizing maize (Zea mays) under cadmium stress: physiological, cytological and genic aspects.

A growing body of evidence suggests that plant root-associated fungi such as dark septate endophytes (DSE) can help plants overcome many biotic and abiotic stresses, of great interest is DSE-plant metal tolerance and alleviation capabilities on contaminated soils. However, the tolerance and alleviation mechanisms involved have not yet been elucidated. In the current study, the regulation and physiological response of Zea mays to its root-associated DSE, Exophiala pisciphila was analyzed under increased soil Cd stress (0, 10, 50, 100 mg kg(-1)). Under Cd stress, DSE inoculation significantly enhanced the activities of antioxidant enzymes and low-molecular weight antioxidants, while also inducing increased Cd accumulation in the cell wall and conversion of Cd into inactive forms by shoot and root specific regulation of genes related to metal uptake, translocation and chelation. Our results showed that DSE colonization resulted in a marked tolerance to Cd, with a significant decrease in cadmium phytotoxicity and a significant increase in maize growth by triggering antioxidant systems, altering metal chemical forms into inactive Cd, and repartitioning subcellular Cd into the cell wall. These results provide comprehensive evidence for the mechanisms by which DSE colonization bioaugments Cd tolerance in maize at physiological, cytological and molecular levels.

Adrenal androgens and androgen precursors-definition, synthesis, regulation and physiologic actions.

The human adrenal produces more 19 carbon (C19) steroids, by mass, than either glucocorticoids or mineralocorticoids. However, the mechanisms regulating adrenal C19 steroid biosynthesis continue to represent one of the most intriguing mysteries of endocrine physiology. This review will discuss the C19 steroids synthesized by the human adrenal and the features within the adrenal that allow production of these steroids. Finally, we consider the effects of these steroids in normal physiology and disorders of adrenal C19 steroid excess.

Identification of small molecules that antagonize diguanylate cyclase enzymes to inhibit biofilm formation.

Bacterial biofilm formation is responsible for numerous chronic infections, causing a severe health burden. Many of these infections cannot be resolved, as bacteria in biofilms are resistant to the host's immune defenses and antibiotic therapy. New strategies to treat biofilm-based infections are critically needed. Cyclic di-GMP (c-di-GMP) is a widely conserved second-messenger signal essential for biofilm formation. As this signaling system is found only in bacteria, it is an attractive target for the development of new antibiofilm interventions. Here, we describe the results of a high-throughput screen to identify small-molecule inhibitors of diguanylate cyclase (DGC) enzymes that synthesize c-di-GMP. We report seven small molecules that antagonize these enzymes and inhibit biofilm formation by Vibrio cholerae. Moreover, two of these compounds significantly reduce the total concentration of c-di-GMP in V. cholerae, one of which also inhibits biofilm formation by Pseudomonas aeruginosa in a continuous-flow system. These molecules represent the first compounds described that are able to inhibit DGC activity to prevent biofilm formation.

Transient neonatal hypocalcemia: presentation and outcomes.

OBJECTIVE: To determine the incidence of moderate-to-severe transient neonatal hypocalcemia in term neonates and to describe the characteristics of affected infants and the outcomes of their management. METHODS: We reviewed medical records of all term infants <31 days of age who presented to Children's Medical Center Dallas from 2001 to 2009 with hypocalcemia (ionized calcium <1.00 mmol/L [4.00 mg/dL]). RESULTS: Seventy-eight infants met criteria. Median (interquartile range) age at admission was 8.0 (7.0-10.0) days, and median duration of admission was 3.0 (2.0-4.0) days. Most infants were male (71.8%) and Hispanic (62.8%). Neonates were generally severely hypocalcemic and hyperphosphatemic. Seventy-five of 78 were hypomagnesemic, and the majority had low or inappropriately normal parathyroid hormone responses. Levels of 25-hydroxyvitamin D were ≤ 62.4 nmol/L (25 ng/mL) in all 42 infants in whom they were determined. All infants responded to therapy of limited duration with 1 or more of the following: calcium supplements, calcitriol, low phosphorus formula, and magnesium supplementation. Neuroimaging did not affect management decisions in any neonate. CONCLUSIONS: Moderate-to-severe late-onset neonatal hypocalcemia is more common in Hispanic and male infants, is often a sign of coexistent vitamin D insufficiency or deficiency and hypomagnesemia, and is readily managed with therapy of limited duration. Neonates presenting with seizures who are found to be hypocalcemic are unlikely to benefit from neuroimaging evaluations.

An overview of nausea/vomiting in palliative medicine.

Nausea, vomiting and retching are among the most distressing symptoms that palliative care may experience. This article presents a brief overview of various medical conditions/treatments that may lead to nausea/vomiting/retching as well as potential mechanisms/neurotransmitters/receptors that may be involved and thus may represent therapeutic targets for antiemetic treatments.

Opioid-induced nausea and vomiting.

Opioids are broad spectrum analgesics that are an integral part of the therapeutic armamentarium to combat pain in the palliative care population. Unfortunately, among the adverse effects of opioids that may be experienced along with analgesia is nausea, vomiting, and/or retching. Although it is conceivable that in the future; combination agents (opioids combined with agents which may nullify emetic effects) currently; nausea/vomiting remains a significant issue for certain patients. However, there exists potential current strategies that may be useful in efforts to diminish the frequency and/or intensity of opioid-induced nausea/ vomiting.

Gout: current insights and future perspectives.

UNLABELLED: Gout is a relatively common inflammatory arthritis that is typically known to occur in middle-aged men. The prevalence of gout appears to be shifting, however, and is increasing in the elderly population. Gout is characterized by severely intense pain and can greatly impact patient quality of life. The study of gout and associated conditions appears to have received research attention in the past, however there is a resurgence in gout interest due to the abundance of novel evidence surrounding its diagnosis, pathophysiology, and treatment. In this review we describe a general overview of gout including its assessment/diagnosis, clinical presentations, predisposing factors, pathophysiology, abortive and prophylactic therapy to control gouty inflammation, and the potential future direction of gout treatment. PERSPECTIVE: Gout is an underappreciated and extremely painful condition. Over the last 2 years new thought on pathophysiology of gout taking into account the inflammasome and new therapeutic agents have changed management strategies.

Pharmacotherapy for fibromyalgia.

Fibromyalgia (FM) is a chronic disorder characterized by multifocal pain and other associated somatic symptoms including fatigue, insomnia, cognitive/memory problems, and even psychological distress. It appears that 2-4% of the general population suffers from FM. FM negatively impacts the physical functioning of its patients, as evidenced by difficulties with multiple daily activities, as well as affecting emotional health, social functioning, and health related quality of life. This review will discuss the potential theories that possibly contribute to the pathogenesis of FM, although the precise mechanism is unknown. The evolution of the assessment of FM will also be examined, with the waning use of tender point examinations and the appearance of new simple, practical diagnostic criteria. Although non-pharmacologic therapeutic options (exercise, education, cognitive-behavioral therapy) have been shown to be extremely effective in FM, the focus of this article will be on pharmacologic strategies. Non-Food and Drug Administration (FDA) approved as well as FDA approved agents will be presented. Each agent's therapeutic "niche" in FM management will be discussed based on its pharmacologic profile, patient responsiveness, and tolerability. Finally a clinical algorithm will be presented for the step-wise management of pain and other associated symptoms of FM.

Duloxetine: a review of its safety and efficacy in the management of fibromyalgia syndrome.

Fibromyalgia (FM) is a chronic disorder characterized by widespread pain and other associated symptoms including fatigue, insomnia, cognitive/memory problems, and even psychological distress. Duloxetine is one of three FDA approved medications (the other two being milnacipran and pregabalin) for the treatment of FM. It has been demonstrated that FM patients possess low central nervous system levels of serotonin and norepinephrine. Duloxetine, which is classified pharmacologically as a serotonin-norepinephrine reuptake inhibitor (SNRI), may be beneficial for FM patients by increasing these levels. This review will touch briefly upon the pathophysiology of FM, diagnostic tools, currently available therapeutic options (both pharmacologic and non-pharmacologic), as well as the pharmacokinetic/pharmacodynamic properties of duloxetine. In addition, the efficacy and safety/tolerability of duloxetine exclusively in FM will be assessed through examination of 5 randomized controlled trials, as well as pooled analyses of current data. Suggestions for a therapeutic niche for duloxetine in FM are discussed based on a presentation of the characteristics of duloxetine.