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To manage ocular redness effectively, health-care practitioners require an understanding of the pathophysiology, clinical features and differential diagnosis of ocular redness, as well as comprehensive knowledge of medical therapies available and their pharmacologic properties. This review aims to provide a clinically relevant summary of the current literature on the mechanism of action, efficacy, and safety of current over-the-counter (OTC) decongestants available for reduction of ocular redness due to minor irritations. Currently marketed OTC products indicated for such use in the United States include topical solutions of tetrahydrozoline 0.05%, naphazoline 0.012% to 0.03%, and brimonidine 0.025%. All 3 agents are adrenergic receptor agonists but vary in their receptor-binding profiles: tetrahydrozoline is a selective α1 receptor agonist; naphazoline is a mixed α1/α2 receptor agonist; and brimonidine is a selective α2 receptor agonist. These OTC decongestants produce vasoconstriction of conjunctival blood vessels, which results in a rapid reduction in ocular redness. In general, ocular adverse events reported in published studies of these OTC decongestants were minimal, mild, and transient, with no significant adverse systemic effects. However, ocular decongestants with α1-adrenergic receptor agonist activity can be associated with loss of effectiveness with continued use (ie, tachyphylaxis) and rebound redness upon treatment discontinuation. In clinical trials of the selective α2-adrenergic receptor agonist brimonidine 0.025%, tachyphylaxis was not observed, and rebound redness was rarely reported.

Transseptal puncture (TSP) is commonly conducted under the guidance of fluoroscopy and/or intracardiac echocardiography (ICE) at the fossa ovalis (FO) to gain percutaneous access to the left atrium for intracardiac procedures. Issues with traditional TSP include: additional vascular access through a sheath, and fluoroscopy exposes patients to ionizing radiation. TSP, if not done appropriately can result in serious complications. We studied the feasibility of optical coherence tomography (OCT) guidance of TSP with ex vivo and in vivo experiments. Results show that OCT can provide detailed structure information to identify FO allowing for safe TSP.

Background Artemisinin resistance observed in Southeast Asia threatens the continued use of artemisinin-based combination therapy in endemic countries. Additionally, the diversity of chemical mode of action in the global portfolio of marketed antimalarials is extremely limited. Addressing the urgent need for the development of new antimalarials, a chemical class of potent antimalarial compounds with a novel mode of action was recently identified. Herein, the preclinical characterization of one of these compounds, ACT-451840, conducted in partnership with academic and industrial groups is presented. Method and Findings The properties of ACT-451840 are described, including its spectrum of activities against multiple life cycle stages of the human malaria parasite Plasmodium falciparum (asexual and sexual) and Plasmodium vivax (asexual) as well as oral in vivo efficacies in two murine malaria models that permit infection with the human and the rodent parasites P. falciparum and Plasmodium berghei, respectively. In vitro, ACT-451840 showed a 50% inhibition concentration of 0.4 nM (standard deviation [SD]: ± 0.0 nM) against the drug-sensitive P. falciparum NF54 strain. The 90% effective doses in the in vivo efficacy models were 3.7 mg/kg against P. falciparum (95% confidence interval: 3.3–4.9 mg/kg) and 13 mg/kg against P. berghei (95% confidence interval: 11–16 mg/kg). ACT-451840 potently prevented male gamete formation from the gametocyte stage with a 50% inhibition concentration of 5.89 nM (SD: ± 1.80 nM) and dose-dependently blocked oocyst development in the mosquito with a 50% inhibitory concentration of 30 nM (range: 23–39). The compound’s preclinical safety profile is presented and is in line with the published results of the first-in-man study in healthy male participants, in whom ACT-451840 was well tolerated. Pharmacokinetic/pharmacodynamic (PK/PD) modeling was applied using efficacy in the murine models (defined either as antimalarial activity or as survival) in relation to area under the concentration versus time curve (AUC), maximum observed plasma concentration (Cmax), and time above a threshold concentration. The determination of the dose–efficacy relationship of ACT-451840 under curative conditions in rodent malaria models allowed prediction of the human efficacious exposure. Conclusion The dual activity of ACT-451840 against asexual and sexual stages of P. falciparum and the activity on P. vivax have the potential to meet the specific profile of a target compound that could replace the fast-acting artemisinin component and harbor additional gametocytocidal activity and, thereby, transmission-blocking properties. The fast parasite reduction ratio (PRR) and gametocytocidal effect of ACT-451840 were recently also confirmed in a clinical proof-of-concept (POC) study., Sergio Wittlin and colleagues report in vivo and in vitro modelling of antimalarial activity and dose-efficacy of a new drug candidate., Author Summary Why Was This Study Done? The limited diversity of chemical mode of action in the global portfolio of marketed antimalarials along with recently observed artemisinin resistance that threatens the current first-line treatment highlights the urgent need for development of new antimalarials. In accordance with target product profiles defined by the Medicines for Malaria Venture ([MMV]; www.mmv.org), a new model of not-for-profit public–private partnership providing guidance to the development of new drugs, ACT-451840, a new chemical class of potent compounds with a novel mode of action, was selected for early development. This manuscript integrates a number of studies performed to characterize preclinically ACT-451840 and illustrates the new antimalarial drug development paradigm. What Did the Researchers Do and Find? This study used in vitro models to investigate compound activity on sexual and asexual blood stages and a mouse model to study the human parasite P. falciparum in vivo. While being fully active against artemisinin-resistant strains, ACT-451840 shares many of the favorable properties of artemisinins like its fast onset of action, activity against all asexual blood stage forms, and a PRR of >4 log per parasite cycle. Pharmacodynamic properties of ACT-451840 were interpreted in two mouse models of malaria with respect to the pharmacokinetic properties, with the objective to establish the portable PK/PD parameters to estimate efficacious exposure. What Do These Findings Mean? Modeling the dose–efficacy relationship of ACT-451840 supported prediction of the human efficacious exposure and therefore laid the groundwork for the new clinical development phases. Confirmed in an experimental human malaria infection model, the properties of ACT-451840, including its fast action observed in in vitro and in vivo models and its transmission-blocking activity, suggest this compound may be able to replace the artemisinin component in artemisinin-based combination therapy.

Neonatal-onset multisystem inflammatory disease (NOMID; also known as chronic infantile neurologic, cutaneous, articular syndrome) (MIM 607115) is the most severe clinical phenotype of a spectrum of autoinflammatory disorders caused by autosomal dominant mutations in CIAS1 or NLRP3 (also called NALP3 or PYPAF1), termed cryopyrin-associated periodic syndromes (CAPS) (1,2). Most patients with milder forms of CAPS (familial cold autoinflammatory syndrome and Muckle-Wells syndrome [MWS]) and NOMID patients present around birth with systemic inflammation, including fever and elevation of acute-phase reactants, conjunctivitis, and an urticaria-like rash. Hearing loss is seen in MWS patients but presents later in life than in NOMID patients. The severe organ-specific manifestations involving the eye, the severe manifestations in the central nervous system (CNS), with aseptic meningitis and ventriculomegaly, and the damage in the bone, with benign, tumor-like lesions, are seen only in NOMID patients (3). Before interleukin-1 (IL-1)–blocking therapy, disease-related progressive organ damage and treatment-related complications resulted in progressive hearing and vision loss, cognitive impairment, physical disability, and infections in NOMID patients and an estimated mortality of up to 20% before adulthood (4). The discovery that NLRP3 is a critical component of an IL-1–activating and secreting complex termed the NLRP3 inflammasome (5–7) suggested IL-1 as a therapeutic target. The pivotal role of IL-1 in causing the clinical manifestations of CAPS was indeed confirmed by clinical studies, initially using the short-acting IL-1 receptor antagonist anakinra (8–10) and, more recently, with 2 long-acting IL-1 inhibitors (11–13). While the short-term effects of IL-1–blocking agents on clinical symptoms and measures of systemic inflammation in the milder forms of CAPS are established, data on the effects of long-term IL-1 suppression on sustained clinical responses with regard to the organ-specific manifestations in NOMID are only recently emerging (14). In this open-label, long-term followup study, we evaluated the efficacy and safety of 36 and 60 months of IL-1–blocking therapy with the IL-1 receptor antagonist anakinra in controlling systemic and organ-specific inflammation and in preventing the progression of organ damage.

Thirty-three N-acyl 1,2,4-dispiro trioxolanes (secondary ozonides) were synthesized. For these ozonides, weak base functional groups were not required for high antimalarial potency against Plasmodium falciparum in vitro, but were necessary for high antimalarial efficacy in Plasmodium berghei-infected mice. A wide range of LogP/D(pH)(7.4) values were tolerated, although more lipophilic ozonides tended to be less metabolically stable.

In four or five chemical steps from the 1,2,4-trioxane artemisinin, a new series of 23 trioxane dimers has been prepared. Eleven of these new trioxane dimers cure malaria-infected mice via oral dosing at 3 x 30 mg/kg. The clinically used trioxane drug sodium artesunate prolonged mouse average survival to 7.2 days with this oral dose regimen. In comparison, animals receiving no drug die typically on day 6-7 postinfection. At only 3 x 10 mg/kg oral dosing, seven dimers prolong the lifetime of malaria-infected mice to days 14-17, more than double the chemotherapeutic effect of sodium artesunate. Ten new trioxane dimers at only a single oral dose of 30 mg/kg prolong mouse average survival to days 8.7-13.7, and this effect is comparable to that of the fully synthetic trioxolane drug development candidate OZ277, which is in phase II clinical trials.

RBx11160 (OZ277) is a promising antimalarial drug candidate that Ranbaxy Laboratories Limited and Medicines for Malaria Venture (MMV) are currently developing as a fixed combination with piperaquine. Here, we describe the in vitro (Plasmodium falciparum) and in vivo (Plasmodium berghei) activities of piperaquine in combination with RBx11160 and artemether. In vitro, both combinations demonstrated a slight tendency towards antagonism with mean sums of fractional inhibitory concentrations (mean Sigma FICs) of 1.5. In vivo, piperaquine and artemether were borderline antagonistic (mean Sigma FIC of 1.4). However, an additive in vivo interaction of piperaquine and RBx11160 (mean Sigma FIC of 1.1) was identified, suggesting that a RBx11160-piperaquine combination therapy in humans should allow each molecule to exert its full antimalarial effect.

Mitochondria have long been recognized as the main source of energy production for the eukaryotic cell. Recent studies have found that the mitochondria have a variety of dynamic functions aside from the production of energy. It communicates bidirectionally with other organelles in order to modulate its energy balance efficiently, as well as maintain homeostasis, ultimately prolonging its own and the cell’s longevity. The mitochondria achieves this level of regulation via specific and common bidirectional chemical messengers, especially involving the endoplasmic/sarcoplasmic reticulum (ER/SR), deoxyribonucleoside triphosphates (dNTP’s), ATP and the generation of reactive oxygen species (ROS). Its communication network is also involved in stress associated events. In this regard, the activation of the Bax family proteins and the release of cytochrome c occurs during cellular stress. The communication can also promote apoptosis of the cell. When mitochondrial abnormalities cannot be dealt with, there is an increased chance that major illnesses like type 2 diabetes, Alzheimer’s disease, and cancer may occur. Importantly, functioning chloroplasts can be found in animals, suggesting conserved chemical messengers during its evolutionary path. The dynamic capacity of mitochondria is also noted by their ability to function anaerobically. Indeed, this latter phenomenon may represent a return to an earlier developmental stage of mitochondria, suggesting certain disorders result from its untimely appearance.

Pervasive developmental disorders, or autism spectrum disorders, are multifaceted and have a high rate of occurrence. Additionally, the origin of Autism appears to be multidimensional and largely unknown. Thus, it would appear novel approaches and concepts are needed in this area of scientific endeavor. In this regard, microbial cells harbored within the human gut and elsewhere are being studied to understand their multi-functional properties and their ability to affect physiological activities in their “host” organism. The communities of approximately 10 trillion microbial cells that live within the gut are involved in functions such as metabolism, nutrition and immune regulation. We and others surmise this microbiota can contribute to disruption of normal activities, causing harmful pathologies such as gastrointestinal complications, obesity, and diabetes and autism. They have the ability to trigger inappropriate immune activation, especially macrophages, which can travel from the gut and penetrate the blood brain barrier and communicate inappropriately with neural cells, altering behavior. Normally these immune cells can enter the brain and become microglia. However, being abnormally stimulated, many more can enter the brain, awakening the sentinel microglia and establishing a proinflammatory state, inducing hypoxia (altering mitochondrial performance). Thus, the microbiome has the potential to extend its influence into the brain, suggesting this may also take place within the parameters of normal activity. In part, the behavioral outcome of such an inappropriate invasion would depend on the region(s) penetrated, manifesting itself with a multidimensional behavioral profile such as occurs in autism.

Neonatal-onset multisystem inflammatory disease is characterized by fever, urticarial rash, aseptic meningitis, deforming arthropathy, hearing loss, and mental retardation. Many patients have mutations in the cold-induced autoinflammatory syndrome 1 (CIAS1) gene, encoding cryopyrin, a protein that regulates inflammation.We selected 18 patients with neonatal-onset multisystem inflammatory disease (12 with identifiable CIAS1 mutations) to receive anakinra, an interleukin-1-receptor antagonist (1 to 2 mg per kilogram of body weight per day subcutaneously). In 11 patients, anakinra was withdrawn at three months until a flare occurred. The primary end points included changes in scores in a daily diary of symptoms, serum levels of amyloid A and C-reactive protein, and the erythrocyte sedimentation rate from baseline to month 3 and from month 3 until a disease flare.All 18 patients had a rapid response to anakinra, with disappearance of rash. Diary scores improved (P0.001) and serum amyloid A (from a median of 174 mg to 8 mg per liter), C-reactive protein (from a median of 5.29 mg to 0.34 mg per deciliter), and the erythrocyte sedimentation rate decreased at month 3 (all P0.001), and remained low at month 6. Magnetic resonance imaging showed improvement in cochlear and leptomeningeal lesions as compared with baseline. Withdrawal of anakinra uniformly resulted in relapse within days; retreatment led to rapid improvement. There were no drug-related serious adverse events.Daily injections of anakinra markedly improved clinical and laboratory manifestations in patients with neonatal-onset multisystem inflammatory disease, with or without CIAS1 mutations. (ClinicalTrials.gov number, NCT00069329 [ClinicalTrials.gov].).

The authors report the first case of propofol use for the control of non-epileptic involuntary movements in a patient with postviral encephalitis. The withdrawal from propofol was associated with re-emergence of involuntary movements. The patient was maintained on propofol infusion for 6 months while a series of medications were used in an attempt to control the movements. The movements were finally controlled with high doses of phenobarbital, diazepam, and olanzapine, and the propofol was slowly weaned.

Objective To study efficacy and safety of escalating doses of canakinumab, a fully human anti-IL-1β monoclonal antibody in the severe cryopyrin-associated periodic syndrome, neonatal-onset multisystem inflammatory disease (NOMID). Methods 6 patients were enrolled in this 24-month, open-label phase I/II study. All underwent anakinra withdrawal. The initial subcutaneous canakinumab dose was 150 mg (or 2 mg/kg in patients ≤40 kg) or 300 mg (or 4 mg/kg) with escalation up to 600 mg (or 8 mg/kg) every 4 weeks. Full remission was remission of patient-reported clinical components and measures of systemic inflammation and CNS inflammation. Hearing, vision and safety were assessed. Primary endpoint was full remission at month 6. Results All patients flared after anakinra withdrawal, and symptoms and serum inflammatory markers improved with canakinumab. All patients required dose escalation to the maximum dose. At month 6, none had full remission, although 4/6 achieved inflammatory remission, based on disease activity diary scores and normal C-reactive proteins. None had CNS remission; 5/6 due to persistent CNS leucocytosis. At the last study visit, 5/6 patients achieved inflammatory remission and 4/6 had continued CNS leucocytosis. Visual acuity and field were stable in all patients, progressive hearing loss occurred in 1/10 ears. Adverse events (AEs) were rare. One serious AE (abscess due to a methicillin-resistant Staphylococcus aureus infection) occurred. Conclusions Canakinumab at the studied doses improves symptoms and serum inflammatory features of NOMID, although low-grade CNS leukocytosis in four patients and headaches in one additional patient persisted. Whether further dose intensifications are beneficial in these cases remains to be assessed. ClinicalTrials.gov identifier NCT00770601.

Background Parkinson's disease (PD) continues to be an important neurological disorder. It is caused by the loss of dopaminergic neurons in the substantia nigra. Dopamine, the neurotransmitter produced from dopaminergic neurons, is a major precursor of endogenous morphine. There are approximately 18 genes associated with PD; their roles have not yet been completely established. PARK2 is a gene that encodes for the protein parkin, and PINK1 is a gene that encodes for PTEN-induced putative kinase 1. Material and methods Our objective was to determine if morphine treatment of HTB-11 cells affects the expression of PINK1 and PARK2. HTB-11 cells were treated with 10-7 M morphine for 2 h and a microarray analysis was conducted. To verify the microarray analysis, 3 Q-PCR trials were run using 10-6 M naloxone, morphine (10-7 M), or a naloxone/morphine mix. Results In both the microarray analysis and the Q-PCR analysis, PARK2 was up-regulated and PINK1 was down-regulated. Conclusions Morphine can affect the expression of PD-associated genes.

Lens flexure and residual astigmatism were evaluated with rigid gas permeable (RGP) contact lenses made in low, medium, and high oxygen permeable (Dk) materials to determine if significant differences would be apparent as lens Dk was changed. Fourteen successful RGP contact lens wearers had their customary lens parameters, including lens thickness, held constant in duplicate pairs made in low (15), medium (60), and high (150) Dk materials. Flexure measured by keratometry over the lenses and residual astigmatism by sphero-cylindrical over-refraction were determined after a 1-week daily wearing period for each lens. No significant differences were found within or between lens materials when comparing magnitude of flexure and residual astigmatism by over-refraction. These results indicate that practitioners can expect lenses across the spectrum of Dk values, such as those evaluated in this study, to perform in a similar manner regarding lens flexure and residual astigmatism.

The purpose of this study was to evaluate visual performance with both spherical rigid gas permeable (RGP) and tonic hydrogel contact lenses. We hypothesized that both visual acuity and performance would be inferior with hydrogel lenses because of dynamic crossed-cylinder effects with eye movement-induced lens rotation. Eighteen subjects (23–45 years) having 0.75–2.50 D of astigmatism in each eye and matching corneal toricity were fitted with both types of lenses (providing at least 20 20 Snellen VA). Seventeen subjects successfully wore each lens type on a full-time basis for 3 weeks prior to testing. Our randomized, crossover study included logMAR threshold visual acuity, contrast sensitivity, and a VDT text-editing task interrupted by a short reading task in upper lateral gaze. Visual performance was assessed by counting errors identified, the error detection rate, and the total number of lines edited. Subjects rated the comfort, quality, and stability of vision just before and after the VDT text-editing task. Subjective ratings were also obtained at the end of the overall wearing period of each lens type in regard to lenswear comfort, visual clarity, and visual stability. Patients chose which pair of lenses to keep after the study. Our analysis of these data indicated no significant differences between threshold visual acuity or pre-post VDT task-related ratings of visual comfort, quality, or stability between the two types of lenses. Contrast sensitivity results were also not different between lens types. The overall ratings at the end of the wearing weeks of each type of lens indicated that tonic hydrogels were better than were RGP lenses for wearing comfort, dryness, and handling, whereas the RGP lenses were rated better for clarity of vision. Stability of vision was rated the same between the two lens types. Seventy-four percent of the subjects chose to continue wearing the tonic hydrogels after the study, whereas 24% chose the RGP lenses. These results suggest that tonic hydrogels can provide equivalent visual performance to spherical RGP contact lenses. Although overall clarity of vision was rated as better with RGP lenses by the subjects, there was a strong final preference for hydrogel lenses, largely due to better overall lens wearing comfort.

Extracts of the medicinal plant Tripterygium wilfordii Hook F (TwHF) have been used in China for centuries to treat a spectrum of inflammatory diseases.To compare the benefits and side effects of TwHF extract with those of sulfasalazine for the treatment of active rheumatoid arthritis.Randomized, controlled trial. A computer-generated code with random, permuted blocks was used to assign treatment.2 U.S. academic centers (National Institutes of Health, Bethesda, Maryland, and University of Texas, Dallas, Texas) and 9 rheumatology subspecialty clinics (in Dallas and Austin, Texas; Tampa and Fort Lauderdale, Florida; Arlington, Virginia; Duncanville, Pennsylvania; Wheaton and Greenbelt, Maryland; and Lansing, Michigan).121 patients with active rheumatoid arthritis and 6 or more painful and swollen joints.TwHF extract, 60 mg 3 times daily, or sulfasalazine, 1 g twice daily. Patients could continue stable doses of oral prednisone or nonsteroidal anti-inflammatory drugs but had to stop taking disease-modifying antirheumatic drugs at least 28 days before randomization.The primary outcome was the rate of achievement of 20% improvement in the American College of Rheumatology criteria (ACR 20) at 24 weeks. Secondary end points were safety; radiographic scores of joint damage; and serum levels of interleukin-6, cholesterol, cortisol, and adrenocorticotropic hormone.Outcome data were available for only 62 patients at 24 weeks. In a mixed-model analysis that imputed data for patients who dropped out, 65.0% (95% CI, 51.6% to 76.9%) of the TwHF group and 32.8% (CI, 21.3% to 46.0%) of the sulfasalazine group met the ACR 20 response criteria (P=0.001). Patients receiving TwHF also had significantly higher response rates for ACR 50 and ACR 70 in mixed-model analyses. Analyses of only completers showed similar significant differences between the treatment groups. Significant improvement was demonstrated in all individual components of the ACR response, including the Health Assessment Questionnaire disability score. Interleukin-6 levels rapidly and significantly decreased in the TwHF group. Although not statistically significant, radiographic progression was lower in the TwHF group. The frequency of adverse events was similar in both groups.Only 62% and 41% of patients continued receiving TwHF extract and sulfasalazine, respectively, during the 24 weeks of the study. Long-term outcome data were not collected on participants who discontinued treatment.In patients who continued treatment for 24 weeks and could also use stable oral prednisone and nonsteroidal anti-inflammatory drugs, attainment of the ACR 20 response criteria was significantly greater with TwHF extract than with sulfasalazine.

Disposable hydrogel contact lenses, which often have a lens care system prescribed for use in support of the lenses, may be worn either on a daily or overnight basis for up to 2 weeks. Since disposable hydrogel lenses are not fundamentally different in basic physical structure and material than nondisposable hydrogel lenses, the physiological and mechanical challenges that they present to the eye are the same (Table I ). The advantage of these lenses and their replacement schedule is the patient wears fresh, clean lenses on a frequent basis to help avoid problems related to lens soilage and lens aging (Table I). The wearing of disposable hydrogel lenses, however, has been reported to be associated with significant problems such as cornea1 ulcers. 1,2 There have also been concerns about the quality of disposable lenses and its role in the development of lens wear-related problems. received in manufacturer’s packaging has been evaluated by several investigators. Lowther3 found nicks, serrated edges, and tears under x 10 magnification, Wadis et al.4 found similar lens quality problems under unspecified magnification, and Veys and Efron’ found both edge-related defects (nicks, tears, roughness, and excess material) and non-edge-related defects (splits, surface blemishes, eccentric optic zones, and lenses found in multiple pieces) when inspected under X 16 magnification (Table 2). The sensitivity in finding visible nicks and tears (“defects”) in disposable lenses is a function of the magnification used to inspect the lenses. This may account for the differences in the results of different investigators. For example, Veys and Efron reported that many defects found under X 16 magnification would not be detectable with the naked eye.5 Veys and Efron also conducted an on-eye evaluation of patient and ocular response to disposable lenses with Address reprint requests to Dr. Christoand without microscopic defects.’ pher Snyder at the University of Alabama Thev studied 29 uatients, who wore a it Birmingham, School of Optometry, ’ University Station, Birmingham, AL pair of disposable lenses for one week 1c7l34 of extended wear where both lenses

The purpose of this clinical study was to evaluate the comparative cleaning efficacy of three surfactant cleaners: BAUSCH & LOMB® SENSITIVE EYES® Daily Cleaner, CooperVision∗ MiraFlow® Extra Strength Daily Cleaner, and Alcon Opti-Cleans® II Daily Cleaner. One hundred seventy-seven patients were entered into this 3-month, double-blind, one-eye/one-eye comparison study at six investigational sites. The results of investigator microscopic examination and laboratory quantitation of total protein deposition indicated no difference between the contact lenses cleaned with SENSITIVE EYES Daily Cleaner and Opti-Clean II (lens material groups 1 and 3) or MiraFlow Extra Strength (lens material groups 1, 3, and 4). Contact lenses from lens material group 2 cleaned with SENSITIVE EYES Daily Cleaner had less total protein than the lenses cleaned with MiraFlow.

Rheumatoid arthritis (RA) is associated with neuroendocrine and immunologic dysfunction leading to rheumatoid cachexia. Although excess proinflammatory cytokines can decrease somatotropic axis activity, little is known about the effects of RA on growth hormone/insulin-like growth factor-1 (GH/IGF-I) axis function. We tested the hypothesis that patients with active RA exhibit decreased GH/IGF-I axis activity. To do so, we conducted a pilot case-control study at a clinical research center in 7 pre- and perimenopausal women with active RA and 10 age- and body mass index-matched healthy women. Participants underwent blood sampling every 20 minutes for 24 hours (8 a.m. to 8 a.m.), and sera were assayed for GH, cortisol, and dehydroepiandrosterone (DHEA). Sera obtained after overnight fasting were assayed for IGF-I, IGF-binding protein (IGFBP)-1, IGFBP-3, C-reactive protein (CRP), interleukin-6 (IL6), glucose, insulin, and lipids. Body composition and bone mineral density were evaluated by DEXA (dual emission x-ray absorptiometry) scans. In patients with RA, mean disease duration was 7.6 ± 6.8 years, and erythrocyte sedimentation rate, CRP, and IL-6 were elevated. GH half-life was shorter than in control subjects (p = 0.0037), with no other significant group differences in GH deconvolution parameters or approximate entropy scores. IGF-I (p = 0.05) and IGFBP-3 (p = 0.058) were lower, whereas IGFBP-1 tended to be higher (p = 0.066), in patients with RA, with nonsignificantly increased 24-hour total GH production rates. There were no significant group differences in cortisol or DHEA secretion. Lean body mass was lower in patients with RA (p = 0.019), particularly in the legs (p = 0.01). Women with active RA exhibit a trend toward GH insensitivity and relatively diminished diurnal cortisol and DHEA secretion for their state of inflammation. Whether these changes contribute to rheumatoid cachexia remains to be determined. Trial registration number NCT00034060.