Remediation of Mild, Acute Radiation Dermatitis Using a Stem Cell-Based Topical: A Real-World Case Report.

INTRODUCTION: Wounds of the skin induced by irradiation involve a disruption of skin homeostasis and an increase in inflammation. Physiological renormalization treatment strategies using the molecules released from stem cells that restore proteostasis and regulate the immune system and reduce inflammation may be effective in treating skin conditions. Previous studies of severe radiation dermatitis found a significant reduction in symptoms using a combination product of the secretome from adipose mesenchymal stem cells and dermal fibroblasts, but mild radiation dermatitis has yet to be studied using this product. CASE PRESENTATION: This is a case report of radiation dermatitis in a patient with an uncommon cutaneous basosquamous cell carcinoma with perineural invasion that warranted radiation therapy. In this study we used S2RM technology, a proprietary combination of stem cell-released molecules from multiple types of skin stem cells, to renormalize homeostasis of the skin, including a renormalization of proteostasis to treat a mild form of radiation dermatitis induced by Intensity Modulated Radiation Therapy. Dramatic reductions in pain, redness, and inflammation, more rapid and complete wound healing, and an overall enhancement of the appearance of the skin were achieved in this patient. DISCUSSION: The current study demonstrates that as part of the palliative care strategies for cancer patients, the simple topical application of S2RM technology is a powerful means to renormalize homeostasis of the skin and remediate mild radiation dermatitis. The reduction of inflammation in the skin is important to reducing systemic inflammation and related comorbidities.

Efficacy of Topical Botanical Treatment of Children With Mild to Moderate Atopic Dermatitis

Objective: The study was conducted to determine the efficacy of the botanical combination incorporated in Kamedis Eczema Therapy Cream (the test product) for children with mild to moderate atopic dermatitis. Design: The study was designed as an interventional, multi-center, double-blind, randomized, controlled study. Setting: Children subjects were a sub-population of the 108 combined population of adults and children evenly randomly divided into three treatment groups: test product, vehicle, and comparator. The vehicle used was the identical test product without the botanical combination while the comparator was a leading OTC brand in the US market. All three groups used the same Kamedis body wash followed by one of the three randomized treatment creams for the affected areas. Participants: Thirty-nine (39) children subjects with uncomplicated, stable, mild to moderate atopic dermatitis were recruited and qualified for the study, 24 female and 15 male, ages varying between 3 and 18. Measurements: Investigators assessed the severity of each subject using the Investigator Global Assessment (IGA), affected Body Surface Area (BSA) extent evaluated parameters at each of the visit days 0, 7, 14, and 28. Subjective symptoms of pruritus and insomnia were evaluated by the patient or their legal guardian. The SCORAD and EASI indexes were calculated based on the collected parameters. Results: The test product demonstrated an improvement in all evaluated and calculated clinical parameters over the vehicle at the end of the treatment duration, proving the validation that the test product is much more effective and beneficial than the vehicle. The test product reached 40% of 'clear' IGA subjects out of the enrolled subjects and 60% out of the 'clear' and 'almost clear' IGA subjects comparing to 8% and 38%, respectively, with the vehicle, presenting a clear advantage over the vehicle. The BSA improvement comparison analysis of the test product over the vehicle yielded P value of less than 0.05, which is statistically significant. The SCORAD and EASI indexes also showed an advantage of the test product versus the vehicle at week 4. Conclusion: The study results validate that the botanical combination is the key factor for the efficacy and improvement of the AD symptoms within this population of children. J Drugs Dermatol. 2019;18(10):1038-1045.

Validation of Botanical Treatment Efficiency for Adults and Children Suffering from Mild to Moderate Atopic Dermatitis

Objective: The study was conducted to determine the efficiency of the botanicals combination incorporated in the Kamedis Eczema Therapy Cream (the tested product) for adults and children suffering from mild to moderate Atopic Dermatitis. Design: The study designed as an interventional, multi-center, double-blind, randomized, controlled study. Setting: Subjects were evenly randomly divided into three treatment groups: tested product, vehicle, and comparator. The vehicle used was the identical tested product without the botanical combination while the comparator was a leading OTC brand in the US market. All three above groups used a similar Kamedis wash for the body and face following by one of the three randomized treatment creams for the affected areas on the face and body. Participants: One hundred and eight (108) subjects with uncomplicated, stable, mild to moderate atopic dermatitis recruited and qualified for the study; 71 females and 37 males, age 3 to 73. Measurements: The investigator assessed the severity of each subject using the Investigator Global Assessment (IGA) and affected body surface area (BSA) at each of the visit days 0, 7, 14, and 28. Results: The tested product demonstrated an improvement in IGA and BSA over the vehicle at every visit across treatment time, proving the validation that the botanical product is much more effective and beneficial than the same product without the botanicals. The tested product as well as the comparator reached exactly the same percentage, 34%, of 'clear' IGA subjects of the enrolled subjects, presenting advantage over the vehicle. The BSA improvement comparison analysis of the tested product over the vehicle yielded statistically significant P value of 0.0369. Conclusion: The study results approve and validate that the botanical combination is the key factor for the efficacy and improvement of the AD symptoms within this study population. J Drugs Dermatol. 2019;18(6):557-561.

Pregnancy rates after pre-implantation genetic screening for aneuploidy are only superior when trophectoderm biopsy is performed on hatching embryos.

PURPOSE: In vitro fertilization with trophectoderm embryo biopsy and pre-implantation genetic screening with comprehensive chromosomal screening (PGS-CCS) for aneuploidy is becoming increasingly more popular. Embryos are cryopreserved and implanted in a subsequent frozen thawed embryo transfer cycle (FET). No studies have investigated differences in pregnancy outcomes by timing of trophectoderm biopsy relative to stages of blastocyst development. METHODS: Retrospective study of all patients (n = 363) at a single IVF center between January 1, 2013 and December 31, 2016 undergoing single embryo transfer with PGS-CCS where embryos were cryopreserved with subsequent FET. Embryo expansion and grading was assessed both at the time of biopsy and transfer. Pregnancy rates were analyzed by embryo expansion and embryo grading. RESULTS: Implantation, clinical pregnancy, and live birth rates improved significantly with increased embryo expansion at the time of embryo biopsy (P < 0.001). Pregnancy loss decreased with increases in embryo expansion prior to biopsy (P < 0.001). Superior live birth rates with PGS-CCS were seen when embryos were hatching at the time of biopsy (p < 0.001). For fresh and frozen embryo transfers without PGS-CCS, embryo expansion did not affect pregnancy outcomes. CONCLUSIONS: PGS-CCS significantly increases implantation and live birth rates only if embryos are hatching at the time of biopsy. The embryo biopsy itself on a non-hatching embryo significantly damages the embryo in ways which are not reflected in future embryo expansion. IVF labs should wait until embryos hatch before performing trophectoderm biopsy.

Initial maternal serum human chorionic gonadotropin levels in pregnancies achieved after assisted reproductive technology are higher after preimplantation genetic screening and after frozen embryo transfer: a retrospective cohort.

PURPOSE: Few published articles have compared initial hCG values across all different types of ART cycles, including cycles with fresh or frozen embryo transfer. No articles have compared initial hCG values in cycles utilizing preimplantation genetic screening (PGS). The purpose of this study is to compare initial hCG values after fresh embryo transfer, frozen embryo transfer, and after PGS. METHODS: This was a single-center retrospective cohort study at an academically affiliated private IVF center. All fresh and frozen embryo transfers between January 2013 and December 31, 2015 were included. We compared mean initial serum hCG values 14 days after oocyte retrieval for fresh cycles and 9 days after frozen embryo transfer. We examined cycles of single embryo transfer (SET) and double embryo transfer (DET). RESULTS: Two hundred elven IVF (fresh embryo transfer), 128 FET (frozen embryo transfer cycles, no PGS), and 111 PGS cycles (ovarian stimulation with embryo cryopreservation, PGS, and frozen transfer in a subsequent estrogen-primed cycle) with initial positive hCG values were analyzed. In patients achieving a positive hCG after SET, initial hCG values were higher after PGS compared to FET (182.4 versus 124.0 mIU/mL, p = 0.02) and IVF (182.4 versus 87.1 mIU/mL, p < 0.001) as well as FET compared to IVF (124.0 versus 87.1 mIU/mL, p < 0.01). After DET, initial hCG values were higher after PGS (222.8 mIU/mL) compared to FET (182.1 mIU/mL, p = 0.02) and IVF (131.1 mIU/mL, p = 0.001). CONCLUSIONS: Our study suggests that initial serum hCG values are higher after using PGS and higher after the transfer of a frozen embryo compared to a fresh embryo. This suggests that initial hCG values relate to the chromosomal status of embryos. Initial hCG values may help determine intervention and monitoring later in pregnancy.

Use of Concomitant FSH with hCG at the Time of Trigger May Improve Success Rates of Couples with Poor Ovarian Response Undergoing Gonadotropin Therapy with IUI.

OBJECTIVE: To investigate if administration of an additional dose of gonadotropins concomitantly to human chorionic gonadotropin (hCG) trigger increases pregnancy rates in patients undergoing intrauterine insemination (IUI) with controlled ovarian hyperstimulation (COH). STUDY DESIGN: This is a retrospective cohort study of all gonadotropin-IUI cycles performed by a single physician in a private practice between January 2012 and September 2013. Control cycles were those in which follicle-stimulating hormone (FSH) was discontinued prior to the day of hCG trigger shot, and study cycles received continuous FSH including the day of hCG trigger shot. A total of 423 cycles from 239 patients were included; 275 (65.5%) were control cycles (137 patients), and 146 (34.7%) were study cycles (102 patients). RESULTS: Pregnancy rates were comparable in both control and study groups (15.27% vs. 15.07%, respectively, p=0.956). There was a 42% increase in multiple gestations in the study group; however, the difference was not statistically significant (p=0.155). Upon multivariate logistic regression, male factor infertility was the only variable that was associated with pregnancy outcomes. CONCLUSION: Continuous administration of FSH including the day of hCG trigger in patients undergoing COH with IUI does not seem to increase pregnancy rates. Our suggested protocol might be beneficial in patients with poor ovarian response.

The presence of multiple gestational sacs confers a higher live birth rate in women with infertility who achieve a positive pregnancy test after fresh and frozen embryo transfer: a retrospective local cohort.

BACKGROUND: After spontaneous conception, the rate of miscarriage is more common in multiple rather than singleton pregnancies. However, the incidence of miscarriage is lower in in-vitro fertilization twin versus singleton pregnancies. Most patients have little understanding of pregnancy outcomes once they achieve a positive pregnancy test. This study investigated the relationship between multiple pregnancy and miscarriage in women with infertility after fresh and frozen embryo transfer. METHODS: Retrospective local cohort study of all consecutive patients undergoing in-vitro fertilization at our institution (n = 1130), fresh or frozen embryo transfer, between January 1, 2008 and December 31, 2012. Patient characteristics (age, body mass index, initial hCG, maximum follicle stimulating hormone levels) and in-vitro fertilization parameters (estradiol levels, eggs retrieved, and endometrial thickness) were collected and statistically analyzed using T-test and Chi-square test (Stata version 10). Linear and logistic regression were used when appropriate. RESULTS: Overall, live birth rate for all cycles was 30.44% and total pregnancy loss was 6.55% - similar for fresh and frozen cycles despite a higher rate of biochemical pregnancies for frozen cycles. Among all pregnant patients, 62.48% had a live birth. Although clinical pregnancy rate was higher for fresh cycles, live birth rates were similar. In pregnancies where multiple sacs were demonstrated on ultrasound, live birth rates were higher despite 31% of patients losing at least one sac. This finding was comparable between fresh and frozen cycles. However, in patients under age 35 and using donor egg, no live birth advantage was seen in patients with multiple sacs. In fact, transferring more than one embryo did not increase live birth rate either. CONCLUSIONS: Despite the many maternal and fetal risks of multiple pregnancies, patients who achieve a positive pregnancy test with fresh and frozen in-vitro fertilization and who have more than one pregnancy sac are more likely ultimately to deliver at least one baby. This finding is true of both fresh and frozen embryo transfer cycles. This pregnancy advantage is not seen in young patients and in patients using donor egg, and single embryo transfer maximizes birth outcomes.

Impact of vitamin D3 dietary supplement matrix on clinical response.

CONTEXT: As a result of research suggesting increased health risk with low serum 25-hydroxycholecalciferol (25(OH)D), health care providers are measuring it frequently. Providers and patients are faced with treatment choices when low status is identified. OBJECTIVE: To compare the safety and efficacy of three vitamin D3 dietary supplements with different delivery matrices. SETTING AND DESIGN: A 12-week, parallel group, single-masked, clinical trial was conducted in Seattle, Washington and Kailua Kona, Hawaii. Sixty-six healthy adults with (25(OH)D) <33 ng/mL were randomly assigned to take one of three D3 supplements, ie, a chewable tablet (TAB), an oil-emulsified drop (DROP), or an encapsulated powder (CAP) at a label-claimed dose of 10,000 IU/day. Actual D3 content was assessed by a third party and the results adjusted based on the actual D3 content administered. Mean change in 25(OH)D/mcg D3 administered; difference in the proportion of D3 insufficient participants (ie, 25(OH)D ≤30 ng/mL) reaching sufficiency (ie, 25(OH)D ≥30 ng/mL); and mean change in serum 1, 25-dihydroxycholecalciferol were measured. RESULTS: In two of the three products tested, the measured vitamin D3 content varied considerably from the label-claimed dose. Differences in 25(OH)D/mcg D3 administered were significantly different between groups (P = .04; n = 55). Pairwise comparisons demonstrated DROP resulted in a greater increase than TAB (P < .05) but not than CAP. TAB was not different from CAP. The proportions reaching sufficiency were: 100% (TAB and CAP) and 80% (DROP) (P = .03 between groups; n = 55). 1, 25-Dihydroxycholecalciferol did not change significantly in any group. CONCLUSIONS: Oil-emulsified vitamin D3 supplements resulted in a greater mean change in serum 25(OH)D concentration, but fewer patients reaching vitamin D sufficiency, than chewable or encapsulated supplements.

Defining the role of bariatric surgery in polycystic ovarian syndrome patients.

Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder in women. To meet PCOS criteria, women must have a combination of hyperandrogenism, anovulation and ultrasound findings. Almost 10% of all reproductive age women worldwide show signs of PCOS. Although women often seek care for gynecological or body image concerns, many PCOS women are at risk for metabolic syndrome (MS). Many of the metabolic consequences are overlooked and undertreated by physicians because these patients tend to be young, reproductive age women. MS and obesity coexist commonly with PCOS. These young women are predisposed to glucose abnormalities and ultimately diabetes mellitus, dyslipidemia and eventually cardiovascular disease. Bariatric surgery can be an effective means of weight loss in PCOS women. Surgical techniques have become safer and less invasive over time and have been found to be effective in achieving significant weight loss. Surgical options have also increased, giving patients more choices. Bariatric surgery may prevent or reverse metabolic syndrome. Bariatric surgery may also have reproductive benefits in PCOS patients. Although bariatric surgery has historically been performed in older, reproductive aged women, it has recently gained favor in adolescents as well. This is of particular importance due to the prevalence of both PCOS and MS in adolescents. Treatment of PCOS and MS certainly requires a combination of medical therapy, psychological support and lifestyle modifications. These treatments are difficult and often frustrating for patients and physicians. Bariatric surgery can be effective in achieving significant weight loss, restoration of the hypothalamic pituitary axis, reduction of cardiovascular risk and even in improving pregnancy outcomes. Ultimately, bariatric surgery should be considered part of the treatment in PCOS women, especially in those with MS.

The "muffin test"--an alternative to the oral glucose tolerance test for detecting impaired glucose tolerance.

OBJECTIVE: The aim of this study was to compare the effectiveness of the "muffin test" (MT) with that of the oral glucose tolerance test (OGTT) in diagnosing impaired glucose tolerance (IGT). METHODS: This is a cross-sectional study in a single academic institution. The participants were 73 women aged 42 to 58 years, less than 36 months after menopause, recruited for the Kronos Early Estrogen Prevention Study Trial. After a 10-hour fasting blood draw, the participants were provided a muffin and a beverage. Two-hour glucose levels were assessed. A subset underwent metabolic testing consisting of an OGTT (n = 12) and a mixed-meal tolerance test (n = 10). The main outcome measures were the prevalence of IGT and 2-hour glucose measurements after each testing method. RESULTS: Two-hour glucose levels were linearly related to fasting values by multivariable linear regression. This association was exaggerated in overweight (body mass index, 25 kg/m2) women (coefficient, 1.43; P < 0.001). Two-hour OGTT and MT glucose levels were comparable (P > 0.05); 2-hour glucose levels after OGTT were slightly lower than after the mixed-meal tolerance test (P < 0.05). CONCLUSIONS: The prevalence of IGT was 11% (8 of 73). Fasting plasma glucose alone would have missed 63% of cases (five of eight cases). The MT demonstrated 100% sensitivity and specificity for diagnosing IGT compared with the gold standard OGTT. This small pilot study should be confirmed in a larger prospective group of participants.

Assessing and treating insulin resistance in women with polycystic ovarian syndrome.

Polycystic ovarian syndrome (PCOS) is a highly prevalent hormonal and metabolic disorder among reproductive aged women worldwide. Women with PCOS have widely varying phenotypes and seek medical care for differing reasons. In addition to concern for menstrual cycle function, ovulation, hirsutism and acne, many PCOS women have abnormal glucose metabolism. While diabetes mellitus and impaired glucose tolerance are easily diagnosed, the diagnosis of and concern for insulin resistance as a precursor disorder is underappreciated. Insulin resistance may be the first important marker of metabolic disease in PCOS women at risk for metabolic syndrome and coronary artery disease.

Reproductive aging and its consequences for general health.

Reproductive aging coincides with endocrine changes that are not solely reproductive in nature and culminates in hypergonadotropic hypogonadism and amenorrhea. These changes are identifiable biochemically regardless of clinical manifestations. Changes in the hypothalamic-pituitary-ovarian axis are associated with changes in other hormonal axes, specifically the adrenal androgen and the somatotropic axis. A large body of literature indicates that reproductive aging is associated with a decline in the somatotropic axis. The interactions between reproductive aging and changes in the adrenal androgen axis are more complex and complicated by age-related declines in the adrenal axis early in the reproductive years. These changes may play an important role in overall health maintenance. Attempts to ameliorate hormonal declines with exogenous hormonal therapy have produced mixed results. Finally, the age-specific timing as well as the rapidity of the changes that occur with reproductive aging seems to have important consequences on metabolism, cardiovascular risk, cognition, bone density, and even mortality.

Acute administration of non-classical estrogen receptor agonists attenuates ischemia-induced hippocampal neuron loss in middle-aged female rats.

BACKGROUND: Pretreatment with 17beta-estradiol (E2) is profoundly neuroprotective in young animals subjected to focal and global ischemia. However, whether E2 retains its neuroprotective efficacy in aging animals, especially when administered after brain insult, is largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: We examined the neuroprotective effects of E2 and two agonists that bind to non-classical estrogen receptors, G1 and STX, when administered after ischemia in middle-aged rats after prolonged ovarian hormone withdrawal. Eight weeks after ovariectomy, middle-aged female rats underwent 10 minutes of global ischemia by four vessel occlusion. Immediately after reperfusion, animals received a single infusion of either E2 (2.25 microg), G1 (50 microg) or STX (50 microg) into the lateral ventricle (ICV) or a single systemic injection of E2 (100 microg/kg). Surviving pyramidal neurons in the hippocampal CA1 were quantified 1 week later. E2 and both agonists that target non-classical estrogen receptors (G1 and STX) administered ICV at the time of reperfusion provided significant levels of neuroprotection, with 55-60% of CA1 neurons surviving vs 15% survival in controls. A single systemic injection of a pharmacological dose of E2 also rescued approximately 50% of CA1 pyramidal neurons destined to die. To determine if E2 and G1 have similar mechanisms of action in hippocampal neurons, we compared the ability of E2 and G1 to modify CA1 pyramidal neuron responses to excitatory inputs from the Schaffer collaterals recorded in hippocampal slices derived from female rats not subjected to global ischemia. E2 and G1 (10 nM) significantly potentiated pyramidal neuron responses to excitatory inputs when applied to hippocampal slices. CONCLUSIONS/SIGNIFICANCE: These findings suggest (1) that middle-aged female rats retain their responsiveness to E2 even after a long period of hormone withdrawal, (2) that non-classical estrogen receptors may mediate the neuroprotective actions of E2 when given after ischemia, and (3) that the neuroprotective efficacy of estrogens may be related to their modulation of synaptic activity in hippocampal slices.

Endometrial thickness, Caucasian ethnicity, and age predict clinical pregnancy following fresh blastocyst embryo transfer: a retrospective cohort.

BACKGROUND: In-vitro fertilization (IVF) with blastocyst as opposed to cleavage stage embryos has been advocated to improve success rates. Limited information exists on which to predict which patients undergoing blastocyst embryo transfer (BET) will achieve pregnancy. This study's objective was to evaluate the predictive value of patient and cycle characteristics for clinical pregnancy following fresh BET. METHODS: This was a retrospective cohort study from 2003-2007 at an academic assisted reproductive program. 114 women with infertility underwent fresh IVF with embryo transfer. We studied patients undergoing transfer of embryos at the blastocyst stage of development. Our main outcome of interest was clinical pregnancy. Clinical pregnancy and its associations with patient characteristics (age, body mass index, FSH, ethnicity) and cycle parameters (thickness of endometrial stripe, number eggs, available cleaving embryos, number blastocysts available, transferred, and cryopreserved, and embryo quality) were examined using Student's T test and Mann-Whitney-U tests as appropriate. Multivariable logistic regression models were created to determine independent predictors of CP following BET. Receiver Operating Characteristic analyses were used to determine the optimal thickness of endometrial stripe for predicting clinical pregnancy. RESULTS: Patients achieving clinical pregnancy demonstrated a thicker endometrial stripe and were younger preceding embryo transfer. On multivariable logistic regression analyses, Caucasian ethnicity (OR 2.641, 95% CI 1.054-6.617), thickness of endometrial stripe, (OR 1.185, 95% CI 1.006-1.396) and age (OR 0.879, 95% CI 0.789-0.980) predicted clinical pregnancy. By receiver operating characteristic analysis, endometrial stripe >or= 9.4 mm demonstrated a sensitivity of 83% for predicting clinical pregnancy following BET. CONCLUSION: In a cohort of patients undergoing fresh BET, thicker endometrial stripe, Caucasian ethnicity, and younger age are positive predictors of clinical pregnancy after fresh BET. These findings may be useful in clinical management of infertile patients undergoing fresh BET cycles.

Mucocele of the appendix causing tubal factor infertility.

OBJECTIVE: To report on the safety of conservative management of a young woman with pseudomyxoma peritonei of appendiceal origin desiring fertility preservation. DESIGN: Case report. SETTING: IVF Center at Tertiary Hospital. PATIENT(S): A 32-year-old woman with primary infertility. INTERVENTION(S): Appendectomy, conservative second-look laparoscopy, and IVF. MAIN OUTCOME MEASURE(S): Persistence of active mucinous lesions in the peritoneal cavity, presence of abnormalities at colonoscopy, and maternal/fetal complications from IVF. RESULT(S): Normal second-look laparoscopy, no evidence of persistent disease, and successful intrauterine twin pregnancy following IVF. CONCLUSION(S): Pseudomyxoma peritonei of appendiceal origin is rare in young female patients. Although traditional therapy in older patients often involves aggressive surgical therapy, this case report demonstrates that patients desiring fertility can be managed conservatively and safely and still maintain successful pregnancy.

Transformational learning: an immersion course on the big island of Hawaii.

Content on integrative healthcare and complementary and alternative medicine is being taught in hundreds of educational programs across the country. Nursing, medical, osteopathic, chiropractic, acupuncture, naturopathic, and other programs are finding creative and innovative ways to include these approaches in new models of education and practice. This column spotlights such innovations in integrative healthcare and CAM education and presents readers with specific educational interventions they can adapt into new or ongoing educational efforts at their institution or programs. We invite readers to submit brief descriptions of efforts in their institutions that reflect the creativity, diversity, and interdisciplinary nature of the field. Please submit to Dr Sierpina at vssierpi@utmb.edu or Dr Kreitzer at kreit003@umn.edu. Submissions should be no more than 500 to 1,500 words. Please include any Web site or other resource that is relevant, as well as contact information.

Psoriasis--pathophysiology, conventional, and alternative approaches to treatment.

Psoriasis is a common T-cell-mediated immune disorder characterized by circumscribed, red, thickened plaques with an overlying silver-white scale. It occurs worldwide, although the incidence is lower in warmer, sunnier climates. The primary cause of psoriasis is unknown. During an active disease state, an underlying inflammatory mechanism is frequently involved. Many conventional treatments focus on suppressing symptoms associated with psoriasis and have significant side effects. This article reviews several of the researched natural approaches to psoriasis treatment, while addressing its underlying cause.

Randomized controlled trial of intraputamenal glial cell line-derived neurotrophic factor infusion in Parkinson disease.

OBJECTIVE: Glial cell line-derived neurotrophic factor (GDNF) exerts potent trophic influence on midbrain dopaminergic neurons. This randomized controlled clinical trial was designed to confirm initial clinical benefits observed in a small, open-label trial using intraputamenal (Ipu) infusion of recombinant human GDNF (liatermin). METHODS: Thirty-four PD patients were randomized 1 to 1 to receive bilateral continuous Ipu infusion of liatermin 15 microg/putamen/day or placebo. The primary end point was the change in Unified Parkinson Disease Rating Scale (UPDRS) motor score in the practically defined off condition at 6 months. Secondary end points included other UPDRS scores, motor tests, dyskinesia ratings, patient diaries, and (18)F-dopa uptake. RESULTS: At 6 months, mean percentage changes in "off" UPDRS motor score were -10.0% and -4.5% in the liatermin and placebo groups, respectively. This treatment difference was not significant (95% confidence interval, -23.0 to 12.0, p = 0.53). Secondary end point results were similar between the groups. A 32.5% treatment difference favoring liatermin in mean (18)F-dopa influx constant (p = 0.019) was observed. Serious, device-related adverse events required surgical repositioning of catheters in two patients and removal of devices in another. Neutralizing antiliatermin antibodies were detected in three patients (one on-study and two in the open-label extension). INTERPRETATION: Liatermin did not confer the predetermined level of clinical benefit to patients with PD despite increased (18)F-dopa uptake. It is uncertain whether technical differences between this trial and positive open-label studies contributed in any way this negative outcome.

Contribution of baroreflex sensitivity and vascular reactivity to variable haemodynamic responses to cocaine in conscious rats.

1. Baroreflex function is critical for short-term arterial pressure regulation and decreased baroreflex responsivity may predict a predisposition to hypertension and sudden cardiac death. In the present study, we assessed whether baroreflex sensitivity (BRS) and/or vascular reactivity covary with haemodynamic responsiveness to cocaine in vascular and mixed responders. 2. We assessed the heart rate index of BRS in resting animals. We examined dose-response relationships to pressor and depressor agents to determine cardiovascular reactivity. Subsequently, rats were given cocaine (5 mg/kg, i.v.) to classify them as vascular or mixed responders. Vascular responders (n=16) were defined as those rats with a substantial (>8%) decrease in cardiac output in response to cocaine owing to a larger increase in systemic vascular resistance. The remaining rats (n=8) were mixed responders because they had smaller increases in vascular resistance and little change or an increase in cardiac output. 3. The BRS determined with angiotensin (Ang) II, but not with phenylephrine, was impaired in mixed responders compared with vascular responders. At equipressor doses, there were significantly greater reductions in cardiac output in vascular responders compared with mixed responders in response to phenylephrine or AngII. Methacholine produced greater decreases in heart rate in vascular responders, suggesting greater muscarinic responsivity. 4. We conclude that differences in vascular reactivity to AngII may contribute to differences in haemodynamic response profiles to cocaine in individual rats. More importantly, the differences in vascular responsivity and BRS do not appear to be primary determinants of haemodynamic response variability.