Biomedical subjects

Susan J Lee

Publications and source records attributed to Susan J Lee.

13 recordsLinked to original sources

PubMed2007

The modified Nail Psoriasis Severity Index: validation of an instrument to assess psoriatic nail involvement in patients with psoriatic arthritis.

OBJECTIVE: Patients with psoriasis and psoriatic arthritis (PsA) commonly have nail involvement. There is no validated psoriatic nail assessment tool. Recently, investigators developed the Nail Psoriasis Severity Index (NAPSI). Beginning with NAPSI, our goal was to validate a psoriatic nail assessment tool for use in clinical trials, and investigate correlations between nail and other PsA features. METHODS: Fingernails of 29 patients with PsA were photographed and scored. Clinical data were collected. Using the original NAPSI, analysis revealed high interrater variability of nail scores. Twenty patients' photographs were regraded using the modified NAPSI (mNAPSI). RESULTS: The mNAPSI scores had excellent interrater reliability (Cronbach's alpha 0.98). Nail scores and physicians' global nail severity visual analog scores showed good inter- and intrarater correlations (Spearman's rho 0.85 and 0.90-0.99, respectively; p < 0.01). Several clinical measures correlated with nail scores. CONCLUSION: The mNAPSI demonstrated excellent interrater reliability and construct validity, and may be a valuable tool.

Adult↗

PubMed2006

New developments in clinically relevant mechanisms and treatment of hyperuricemia.

The prevalence of gout has increased markedly in the United States in the past two decades, and new treatments for hyperuricemia are being developed. Recent molecular identification of urate transporter-1 (URAT1) as the central mediator of renal urate reabsorption has provided novel understanding of the pathogenesis of hyperuricemia, and the target site for current and possibly future primary uricosuric agents. Recent studies have also highlighted uricosuric effects of several drugs (losartan, atorvastatin, fenofibrate) that are prescribed for primary indications other than hyperuricemia. The niche of these agents in current management of hyperuricemia is discussed. We also review the ongoing development of recombinant uricase preparations and of novel xanthine oxidase inhibitors exemplified by febuxostat. These agents should provide novel options for patients with chronic, refractory gout and hyperuricemia, particularly in association with allopurinol hypersensitivity and renal insufficiency.

Febuxostat↗

PubMed2006

4. Autoimmunity, vasculitis, and autoantibodies.

Autoimmune diseases are distinct clinical syndromes characterized by various alterations in normal immune responsiveness, such that there is a loss of tolerance to particular host constituents. In most cases, despite years of intense investigation, the etiopathogenic antigens initiating these systemic inflammatory conditions remain undefined. However, a great deal has been learned about the changes in components of the immune response relevant to the propagation and sustenance of these often chronic disorders. In addition, various hormonal, environmental, physiologic, and other influences that affect their expression have been identified. The expression and ultimate clinical outcome of autoimmune diseases usually relate to inflammation-related damage to the target organ with subsequent dysfunction. Certain immune conditions, such as autoimmune thyroid disease, largely affect a single organ, whereas others, such as systemic lupus erythematosus, heterogeneously affect sundry organ systems. Autoantibodies directed against normal host antigens are a common feature of many autoimmune diseases. In some cases they are pathogenic, whereas in others they serve as markers for organ involvement or outcomes. Clinical descriptions of autoimmune diseases date back many decades in some cases. Recent efforts at formulating classification criteria have allowed clearer distinctions and more accurate stratification. Greater understanding of the immunopathogenesis of autoimmune conditions has led to the development and introduction into the clinic of novel immunomodulatory therapies and treatment paradigms that have substantially improved the outcomes for patients affected by these serious conditions.

Animals↗

PubMed2006

Risk factors associated with presenting for abortion in the second trimester.

OBJECTIVE: To determine factors associated with delay of induced abortion into the second trimester of pregnancy. METHODS: Using audio computer-assisted self-interviewing, 398 women from 5 to 23 weeks of gestation at an urban hospital described steps and reasons that could have led to a delayed abortion. Multivariable logistic regression identified independent contributors to delay. RESULTS: Half of the 70-day difference between the average gestational durations in first- and second-trimester abortions is due to later suspicion of pregnancy and administration of a pregnancy test. Delays in suspecting and testing for pregnancy cumulatively caused 58% of second-trimester patients to miss the opportunity to have a first-trimester abortion. Women presenting in the second trimester experienced more delaying factors (3.2 versus 2.0, P < .001), with logistical delays occurring more frequently for these women (63.3% versus 30.4%, P < .001). Factors associated with second-trimester abortion in logistic regression were prior second-trimester abortion, delay in obtaining state insurance, difficulty locating a provider, initial referral elsewhere, and uncertainty about last menstrual period. Factors associated with decreased likelihood of second-trimester abortion were presence of nausea or vomiting, prior abortion, and contraception use. CONCLUSION: Abortion delay results from myriad factors, many of them logistical, such as inappropriate or delayed referrals and delays in obtaining public insurance. Public health interventions could promote earlier recognition of pregnancy, more timely referrals, more easily obtainable public funding, and improved abortion access for indigent women. However, accessible second-trimester abortion services will remain necessary for the women who present late due to delayed recognition of and testing for pregnancy. LEVEL OF EVIDENCE: II-2.

Abortion, Induced↗

PubMed2006

Recent developments in diet and gout.

PURPOSE OF REVIEW: Gout is the most common inflammatory arthritis in men, affecting approximately 1-2% of adult men in Western countries. United States gout prevalence has approximately doubled over the past two decades. In recent years, key prospective epidemiological and open-labeled dietary studies, coupled with recent advances in molecular biology elucidating proximal tubular urate transport, have provided novel insights into roles of diet and alcohol in hyperuricemia and gout. This review focuses on recent developments and their implications for clinical practice, including how we advise patients on appropriate diets and alcoholic beverage consumption. RECENT FINDINGS: Studies have observed an increased risk of gout among those who consumed the highest quintile of meat, seafood and alcohol. Although limited by confounding variables, low-fat dairy products, ascorbic acid and wine consumption appeared to be protective for the development of gout. SUMMARY: The most effective forms of dietary regimen for both hyperuricemia and gout flares remains to be unidentified. Until confirmed by a large, controlled study, it is prudent to advise patients to consume meat, seafood and alcoholic beverages in moderation, with special attention to food portion size and content of non-complex carbohydrates which are essential for weight loss and improved insulin sensitivity.

Beer↗

PubMed2005

Fetal pain: a systematic multidisciplinary review of the evidence.

CONTEXT: Proposed federal legislation would require physicians to inform women seeking abortions at 20 or more weeks after fertilization that the fetus feels pain and to offer anesthesia administered directly to the fetus. This article examines whether a fetus feels pain and if so, whether safe and effective techniques exist for providing direct fetal anesthesia or analgesia in the context of therapeutic procedures or abortion. EVIDENCE ACQUISITION: Systematic search of PubMed for English-language articles focusing on human studies related to fetal pain, anesthesia, and analgesia. Included articles studied fetuses of less than 30 weeks' gestational age or specifically addressed fetal pain perception or nociception. Articles were reviewed for additional references. The search was performed without date limitations and was current as of June 6, 2005. EVIDENCE SYNTHESIS: Pain perception requires conscious recognition or awareness of a noxious stimulus. Neither withdrawal reflexes nor hormonal stress responses to invasive procedures prove the existence of fetal pain, because they can be elicited by nonpainful stimuli and occur without conscious cortical processing. Fetal awareness of noxious stimuli requires functional thalamocortical connections. Thalamocortical fibers begin appearing between 23 to 30 weeks' gestational age, while electroencephalography suggests the capacity for functional pain perception in preterm neonates probably does not exist before 29 or 30 weeks. For fetal surgery, women may receive general anesthesia and/or analgesics intended for placental transfer, and parenteral opioids may be administered to the fetus under direct or sonographic visualization. In these circumstances, administration of anesthesia and analgesia serves purposes unrelated to reduction of fetal pain, including inhibition of fetal movement, prevention of fetal hormonal stress responses, and induction of uterine atony. CONCLUSIONS: Evidence regarding the capacity for fetal pain is limited but indicates that fetal perception of pain is unlikely before the third trimester. Little or no evidence addresses the effectiveness of direct fetal anesthetic or analgesic techniques. Similarly, limited or no data exist on the safety of such techniques for pregnant women in the context of abortion. Anesthetic techniques currently used during fetal surgery are not directly applicable to abortion procedures.

Abortion, Induced↗

PubMed2005

Differential stress reactivity in intact and ovariectomized prepubertal and adult female rats.

The pubertal development of the hypothalamic-pituitary-adrenal (HPA) axis has received relatively little experimental attention. As puberty is marked by an increase in the susceptibility to various psychiatric disorders that may be related to HPA dysfunction, it is imperative to elucidate the pubertal development of this neuroendocrine axis. To date, the limited research in this area has been conducted primarily on males. Presently, we investigated stress responsiveness, as measured by both stress hormones (e.g., corticotropin (ACTH) and corticosterone) and gonadal steroids, in intact and ovariectomized prepubertal and adult female rats before and after a 30-min session of restraint stress. We report here that intact prepubertal females exhibit an extended corticosterone stress response (30-45 min longer) compared to intact adults. Moreover, ovariectomized prepubertal females continue to exhibit a prolonged stress-induced corticosterone and progesterone response compared to ovariectomized adults, indicating these protracted responses prior to puberty are independent of ovarian hormones. ACTH levels were not significantly different between intact and ovariectomized prepubertal and adult animals at all the post-stress time points measured, suggesting that the prolonged corticosterone response in prepubertal females is due to an enhanced sensitivity to ACTH at the level of the adrenal cortex. Taken together, these data indicate that stress reactivity changes dramatically during puberty in females. Furthermore, these data demonstrate additional development of the HPA axis during pubertal maturation, resulting in a more quickly terminated stress response in adulthood.

Adrenocorticotropic Hormone↗

PubMed2005

Adverse reactions to biologic agents: focus on autoimmune disease therapies.

In recent years, a growing number of biologic agents have become available for the treatment of various autoimmune, neoplastic, cardiovascular, infectious, allergic, and other conditions. Their introduction has resulted in marked clinical improvements for many patients. Nevertheless, a variety of adverse reactions have been observed with these agents. Because many biologic agents affect key components of sundry physiologic processes, a number of important adverse reactions might be considered mechanism based. Other adverse reactions relate to the agent rather than the target, including hypersensitivity reactions. As a means of exploring the spectrum of potential adverse effects related to biologic agents and their mechanisms, this review will focus on the experience to date with biologic agents used for the treatment of autoimmune disorders. An understanding of the spectrum and types of reactions possible with biologic agents, as well as the mechanisms underlying such reactions, will help clinicians use them optimally.

Abatacept↗

PubMed2005

Factors affecting rheumatoid arthritis patients' decisions to participate in clinical trials.

OBJECTIVE: To delineate the personal, psychosocial, and disease-related factors that may influence rheumatoid arthritis (RA) patients' decisions to participate in clinical trials. METHODS: A total of 191 patients with RA were asked to participate in this survey. The questionnaire collected information on demographics, RA disease-related factors, and the importance of several factors that might influence patients' willingness to participate in clinical trials. Patients were then asked if they would consider participating in a hypothetical study. RESULTS: Participants were 88% female with a mean age of 40.5 years. The ethnic composition was 57% Hispanic, 25% Caucasian, 12% Asian, and 6% African American, with 71% having a family income < $20,000/year. Factors that patients considered important for participation in a clinical study included: the opportunity to help others, the possibility of improved health, early access to new therapy, the availability of free treatments, unknown side effects of the study drug, and the need to stop current therapy. There were strong correlations between the rank order importance weights between Hispanics and Caucasians, suggesting fundamental similarities in preferences. The most important factor was the opportunity to help others. In general, the more important factors were associated with preferences for trial participation. CONCLUSION: This questionnaire identified factors that may affect RA patients' willingness to participate in a study. Patient participation in trials is driven by diverse factors that include altruism and the opportunity for healthcare and improved health. Consideration of these factors may facilitate the inclusion of more diverse patient populations into trials and enhance the applicability of trial results.

Adult↗

PubMed2004

Testosterone cannot activate an adult-like stress response in prepubertal male rats.

The pubertal maturation of the hypothalamic-pituitary-adrenal (HPA) axis has received relatively little experimental attention. The present set of experiments sought to extend our understanding of the pubertal stress response by measuring corticotropin (ACTH), corticosterone, and testosterone levels in prepubertal and adult male rats exposed to a single 30-min session of restraint stress. We show that ACTH and corticosterone levels in prepubertal males take significantly longer to return to baseline after termination of the stressor compared to adults. These data indicate that prepubertal males demonstrate a more prolonged stress response compared to adults after a single acute stressor with both psychogenic and neurogenic components. As testosterone has been shown to reduce the stress response in adulthood, we next investigated whether the relatively low levels of circulating testosterone in prepubertal males mediated their protracted stress response. Data collected from additional experiments revealed that prepubertal males treated with adult-like physiological levels of testosterone still exhibited an extended stress response compared to similarly treated adults. These results indicate that the stress response demonstrated by adult males cannot be mimicked or activated in prepubertal males by mere supplementation of testosterone. Thus, we conclude that the HPA neuroendocrine axis is further shaped during pubertal development to allow for the emergence of a more tightly regulated stress response in adulthood.

Adaptation, Physiological↗

PubMed2004

Targeting of TAK1 by the NF-kappa B protein Relish regulates the JNK-mediated immune response in Drosophila.

The molecular circuitry underlying innate immunity is constructed of multiple, evolutionarily conserved signaling modules with distinct regulatory targets. The MAP kinases and the IKK-NF-kappa B molecules play important roles in the initiation of immune effector responses. We have found that the Drosophila NF-kappa B protein Relish plays a crucial role in limiting the duration of JNK activation and output in response to Gram-negative infections. Relish activation is linked to proteasomal degradation of TAK1, the upstream MAP kinase kinase kinase required for JNK activation. Degradation of TAK1 leads to a rapid termination of JNK signaling, resulting in a transient JNK-dependent response that precedes the sustained induction of Relish-dependent innate immune loci. Because the IKK-NF-kappa B module also negatively regulates JNK activation in mammals, thereby controlling inflammation-induced apoptosis, the regulatory cross-talk between the JNK and NF-kappa B pathways appears to be broadly conserved.

Animals↗

PubMed2003

Secondary immune deficiencies associated with biological therapeutics.

Biological therapeutics have been utilized in the past several years for the treatment of various autoimmune, cardiovascular, and neoplastic conditions. As these agents target both pathologic and physiologic components of inflammatory and immune systems, the scientific community has been challenged to identify potential secondary immune deficiencies associated with their use. This article will focus on biological agents used for the treatment of rheumatoid arthritis, including tumor necrosis factor-a inhibitors, cytotoxic T lymphocyte-associated antigen-4 (CTLA-4 Ig), rituximab, and interleukin-1 receptor agonist (IL-1Ra). Both clinical and in vitro studies have been done to explore the potential immunomodulatory and immunosuppressive effects of these agents.

Abatacept↗

PubMed2002

Serotonin mediates CA1 spine density but is not crucial for ovarian steroid regulation of synaptic plasticity in the adult rat dorsal hippocampus.

The activity of the serotonin (5-hydroxytryptamine, 5-HT) system is sensitive to estradiol and progesterone. During the ovarian cycle, dendritic spines on CA1 pyramidal neurons of the dorsal hippocampus are increased by estradiol and later decreased by progesterone. We sought to determine whether 5-HT is involved in maintaining CA1 spine density and/or in steroid regulation of synaptic plasticity in dorsal hippocampus. Ovariectomized rats were treated (sc) over 10 days with the tryptophan hydroxylase inhibitor parachlorophenylalanine (pCPA) to deplete 5-HT, followed by estradiol benzoate on days 10 and 11. A subset of animals received progesterone on day 12. The day after the last treatment, rats were perfused and brains were processed for Golgi impregnation. Separate groups were processed for radioimmunocytochemistry (RICC) for the spine-associated protein, spinophilin, or high-performance liquid chromatography (HPLC) for monoamine analysis. Golgi and RICC data indicate that CA1 apical spine density was significantly decreased by pCPA (17-20%). Estradiol increased spine density in both saline- and pCPA-treated rats compared to respective controls (30%); however, pCPA animals maintained significantly fewer spines. No differences in spine densities were observed between saline- and pCPA-treated rats given estradiol and progesterone. Depletion of 5-HT by pCPA was confirmed in the CA1 (-90%) and dorsal raphe (-80%) by HPLC analysis. While 5-HT depletion was associated with a 57% decrease in CA1 norepinephrine (NE), there was no difference in dorsal raphe NE. Thus, whereas 5-HT is involved in maintaining spine density in the adult female rat CA1, it is not crucial for steroid-mediated plasticity. 5-HT-regulated spines/synapses may represent distinct populations from those modulated by estradiol and progesterone in dorsal hippocampus.

Animals↗