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Current understanding of steroid treatments for keloids is in regards to modulation of inflammation, proliferation, and apoptosis, with no in vivo study on the latter. Using a nude mouse model, we investigated whether triamcinolone acetonide (TA) injections induce keloids regression through enhancing apoptosis.Thirty-six keloid specimens (1 × 1 cm) were harvested from 6 patients and separated into sets of 2 from the same patient: no treatment and intralesional TA injection (0.4 mg/mL/kg) at 8 weeks of postimplantation. One set was implanted in each of 18 randomly selected nude mice, which were separated into 3 groups based on time of keloid harvesting after treatment: group A, 2 weeks; group B, 8 weeks; and group C, 14 weeks. Each group had 1 set of specimen from each patient. Histological staining was performed with hematoxylin and eosin stain. Immunohistochemistry staining was performed for human-prolyl 4-hydroxylase (hPH4) and caspase 3 protein, along with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay.All keloid specimens survived, with no noted overgrowth. Hematoxylin and eosin staining revealed dense extracellular matrix and viable fibroblasts, and hPH4 immunohistochemistry revealed strong expression, demonstrating keloid viability. Caspase 3 protein and TUNEL expressions were significantly increased in the treatment versus control groups, demonstrating that TA injections induced apoptosis.Triamcinolone acetonide intralesional injections significantly increased apoptosis in keloids, represented by increased caspase 3 protein and TUNEL expressions, supporting that steroids suppress keloids in part owing to enhancement of apoptosis.

Omalizumab has been recognized to be effective in the treatment of chronic spontaneous urticaria (CSU). The Italian Medicines Agency authorizes two omalizumab courses, only for patients with CSU unresponsive to antihistamines, and this schedule may limit omalizumab use. Unfortunately, in the majority of CSU, the schedule is unsatisfactory because symptoms usually recur shortly after discontinuation of treatment. A case of a patient needing more than two treatment courses with omalizumab is reported, in order to discuss the rationale for its long-term use. Patient had needed systemic steroids almost continuously for 4 years. Two severe glucocorticoid-associated adverse events (GAEs) occurred during long-term treatment. Omalizumab 300 mg monthly was started with immediate disappearance of the urticarial lesions. Beneficial effects waned shortly after discontinuation of treatment, and further steroid use was needed. A second omalizumab course showed the same clinical pattern, with prompt response and recurrence of symptoms after suspension. Therefore, we decided to repeat the 6 months omalizumab treatment as soon as symptoms recurred, to avoid further emergency steroid treatments and GAEs. This experience suggests that long-term use of omalizumab could be useful. Evidences show that omalizumab is effective and safe for re-treatment and long-term use of responding patients after recurrence.

Importance Evaluating the treatment outcomes of diabetic macular oedema (DMO) in routine clinical practice provides data for comparison with those of clinical trials. Background Phase 3 clinical trials of vascular endothelial growth factor (VEGF) inhibitors for DMO have reported significant improvements in visual acuity (VA) not previously reported with laser and steroid treatments. Design Retrospective analysis of observational data from routine clinical practice. Participants Eyes receiving treatments for DMO tracked in the Fight Retinal Blindness! Registry. Methods We analysed 510 eyes (347 patients) that started DMO treatment between 2009 and 2014. Main outcome measures Changes in DMO treatment patterns and mean change in VA (letters logMAR) and central subfield thickness (CST) 5 years after starting treatment. Results Treatment choice for DMO changed to predominantly VEGF inhibitors from 2009 to 2014. A total of 238 eyes (47%) were followed for at least 5 years. The mean VA at the start of treatment improved from 2009 (58 letters) to 2014 (68 letters) while mean VA change at 5 years were + 4.5 and + 5.3 letters for eyes starting treatment in 2009 and 2014, respectively. The mean CST dropped from 401 μm at baseline to 314 μm at 5 years. Eyes received a median of four injections in the first, two in the second, third and fourth and three in the fifth years. Conclusions and relevance Changing the treatment of DMO from macular laser and intravitreal triamcinolone to VEGF inhibitors from 2011 onwards was associated with better VA outcomes, part of which were due to better VA at the start of treatment. The outcomes of treatment in eyes in real-world practice were, however, worse than those reported by clinical trials, likely because they were undertreated.

We analyzed 356 patients with idiopathic sudden sensorineural hearing loss treated with hyperbaric oxygen therapy and systemic steroids (n = 161), systemic steroids alone (n = 160), or intratympanic and systemic steroids (n = 35). The main outcome measure was the hearing recovery rate. The effect of other variables, including the initial averaged 5-frequency hearing level, patient age, interval between the onset of symptoms and treatment, presence of vertigo as a complication, presence of diabetes mellitus, smoking history, and presence of hypertension, on the hearing recovery rate was also evaluated. The overall hearing recovery rate was significantly higher for the patients treated with hyperbaric oxygen therapy and systemic steroids than for those treated with systemic steroids alone (p < 0.001) or systemic and intratympanic steroids (p < 0.001). The presence of vertigo negatively affected hearing recovery. Our findings suggest that hyperbaric oxygen therapy confers a significant additional therapeutic benefit when used in combination with steroid therapy for idiopathic sudden sensorineural hearing loss.

People all over the world should work in each individual against global warming due to greenhouse gas that is made up of a majority of carbon dioxide. On the other hand chloro-fluoro-carbon (CFC) was used with pressured metered-dose inhaler steroid therapy, but CFC became banning the use because of ozone depleting substance. Hydrofluorocarbon (HFA134a, tetra-fluoro-methane) is used as alternative CFC until now. Less-famously hydro-fluoro-carbon (HFA134a) have 1300-fold (mole ratio) energy of heat-trapping relative to carbon dioxide.On an extremely localized story, we derived substantial gravity of carbon dioxide from sales total of pressured metered-dose inhaler (pMDI) steroid drugs for the year in Japan. The amount of total sales of inhaled corticosteroid drugs on annual 2006 year was 320 hundred-millions yen. 88 hundred-millions yen (27.4% for total ICS sales) was accounted for pressured metered-dose inhaler steroid. Now in Japan there are three kinds of pressured metered-dose inhaler steroid drugs which all use tetra-fluoro-methane (HFA134a). In fact total gravity of tetra-fluoro-methane (HFA134a) from pressured metered-dose inhaler steroid for annual 2006 year was 19.7 t and substantial gravity of carbon dioxide was 10.8 thousand ton. As total gravity of carbon dioxide production throughout the year in Japan was 13 hundred-million ton. Therefore substantial gravity of carbon dioxide by steroids pressured metered-dose inhaler was very small (0.001%) compared to total carbon dioxide production in Japan. Until today carbon-dioxide reducing make very slow progress, for that reason medical service worker unexceptionally should exert an effort for carbon-dioxide reduction if only slightly through the daily clinical examination. Keywords: HFA, HFC, ICS, pMDI, CO2, Greenhouse gas, Global warming, Montreal protocol, Kyoto Protocol

Glucocorticoids are commonly prescribed medications associated with significant mortality and morbidity, even when used at physiological dosages. The endogenous glucocorticoids are secreted in a complex rhythm consisting of both a daily circadian rhythm and a more rapid and dynamic ultradian rhythm that is highly conserved in nature. Current therapeutic options attempt to target the circadian aspects of this rhythm but do not take into account the oscillating ultradian pulsatility.This article analyzes English-language literature on Pubmed and discusses the physiology and evidence behind the importance of different patterns of glucocorticoid presentation on gene regulation, animal responses and clinical significance.There is compelling evidence for pulsatility being an important factor in hypothalamic pituitary adrenal (HPA) axis regulation and tissue responses to glucocorticoids. Different patterns of gene regulation and neural and behavioral responses are seen dependent upon the pattern of glucocorticoid presentation. Disease states are associated with disordered HPA ultradian activity. Glucocorticoid treatments have significant risk/benefit issues. It is now time to go back to first principles and think about the physiology and patterns of drug presentation in glucocorticoid-based therapeutics.

Acute pancreatitis can be encountered as a rare complication of thrombotic thrombocytopenic purpura and it has been associated with recurrent thrombotic thrombocytopenic purpura. In this report, we present a case of thrombotic thrombocytopenic purpura closely followed for recurrent acute pancreatitis attacks and having a lethal clinical picture due to splenic vein rupture in spite of plasmapheresis and steroid treatments.

Purpose This study examined the audiometric findings following steroid treatment for autoimmune inner ear disease (AIED), which is characterized by bilateral subacute hearing loss, using oral and intratympanic treatment. Method The charts of 9 patients with AIED who had been seen in the Saint Louis University School of Medicine's clinic between 2004 and 2011 were reviewed, with special focus on audiometric results. Results The majority of patients benefited from treatment for AIED. Four patients (6 ears) received intratympanic therapy as part of their treatment. Conclusion Patients with AIED appeared to benefit from a clinical pathway using a prolonged course of oral steroids, followed by a trial of intratympanic steroids and/or immunosuppresants for refractory cases.

TO THE EDITOR: Although much is known about hypereosinophilic syndrome (HES), the notable discovery of a few genetic rearrangements, such as FIP1L1/PDGFRA (F/P) and TEL/PDGFRB, and the identification of a phenotypically aberrant clonal T lymphocyte brought a new paradigm to HES. As a result, multidisciplinary groups of hematologists and scientists have created more stratified treatment guidelines for patients with HES. However, more than half of patients with HES are still classified as undefined under the current diagnostic criteria and the best course of treatment for these patients remains unclear, especially after initial steroid treatments fail. Here, we present two cases of undefined HES who were successfully treated with cyclosporine A (CsA) after corticosteroid treatment failed.

Background Medical practice in the media is usually far from reality. Thus, the viewer may be led astray. The world-famous fictional Dr House has to face a difficult diagnosis every week. His practice does not seem to reflect reality. The aim of this study was to assess the diagnosis strategy involved in this television program. Methods An observer has previewed the 2011 season. The episode running time, the patient's age and sex, the list of all investigations and interventions, the final diagnosis, and the patient's outcome were collected. Number and proportion of French viewers for each episode were recorded. Results We analyzed 18 episodes. The median running time was 42.5 (42.1-43.2) minutes. Main patient characters were 12 men (66%) and 6 women (33%); the average age was 31 (22-38) years. There were 225 investigations or interventions reported, averaging 14 (9-15) per episode, representing one examination every 3.1 (2.9-4.8) minutes. The most frequently prescribed investigations were magnetic resonance imaging (MRI; 13; 72%), blood sample (11; 61%), and biopsy (10; 56%). The most frequent interventions were surgery, anti-infectious treatments, and steroid treatments (9 each; 50%). Two patients (11%) died. The median number of spectators was 8.4 (8.1-8.7) million, corresponding to 33% (33%-34%) of the French national audience. Conclusion The population and the examination strategies used by Dr House were unrealistic. Because of this distortion, patients may not understand, nor accept the delay, the investigation choices, the intervention costs, risks, nor failures of a daily medical practice. Physicians should be aware of this "information bias."

We report the case of a 57-year-old man who presented bilateral subacute and painless optic neuropathy after meningopolyradiculitis revealing a primary human immunodeficiency virus infection. Both antiretroviral and steroid treatments were ineffective. Clinical symptoms and evolutive pattern were consistent with a mechanism of microvascular ischaemia of the optic nerve head. Optic neuropathies related to HIV infection are rare compared to those resulting from opportunistic infections. There are several pathophysiological mechanisms involved.

Risk factors for asthma death were evaluated from pulmonary function tests during stable period. Subjects were divided into three groups. The first group was asthma death group, in which 16 patients(10 males, 6 females) died with acute asthma attacks during last 20 years in our hospital and had performed pulmonary function tests before death, age and duration of asthma being 14.7±4.9 years-old, 12.8±5.9 years(mean±SD) respectively. The second group was severe group, in which 49 patients (29 males, 20 females) had severe asthma attacks with cyanosis between 1988 and 1991 year, and had performed pulmonary function test within one year before such episodes, age and duration of asthma being 15.2±5.2 years-old, 11.9±4.9 years respectively. The third group was mild group, in which 84 patients (56 males, 28 females) under good control, neither had severe attacks nor hospitalization, age and duration of asthma being 13.1±4.4 years-old, 9.6±4.8 years respectively. Pulmonary function tests were performed at 19.7±12.5 months before death in asthma death group and at 4.3±3.8 months before severe attacks in severe group.The values of FEV1.0% in asthma death group, severe group, and mild group were 67.3±11.3%, 70.0±11.9%, and 81.6±8.0% respectively, while significant lower FEV1.0% were observed in severe group (p

Summary A study involving 60 light-horse mares was conducted both to evaluate the response of mares to injectable progester- one or altrenogest and to determine ifestradiol in combination with either progestogen provided any added benefit. Treatments were initiated at either early estrus, late estrus, early diestrus, mid-diestrus or late diestrus in order to assess the effect of stage of cycle at onset of treatment. Within each of these stages of the cycle, mares were randomly assigned to 1 of 4 treatments: 150 mg progesterone injected i.m. (P); 150 mg progesterone + 10 mg estradio11713 injected i.m. (P+); .044 mg altrenogest per kg body weight orally (A); and .044 mg per kg body weight orally plus 10 mg estradiol 1713 i.m. (A+). All treatments were given daily for 7 days with 10 mg PGFaCt given on day 7 to all mares. The number of mares ovulating by day 14 after treatment (N=15/group) was 13, 7,11 and 8 forA, A+, P and P+, respectively. The response of mares to progesterone and altrenogest was similar. Fewer (Pi0.05) mares given combined steroid treatments ovulated within 14 days (15 of 30) than those given progestogen treatments. Stage of cycle had no affect (Pi0.05) on response of mares ovulating within 14 days or after 14 days of treatment. Mares that ovulated within 14 days of treatment had larger foUieles after progestogen treatment than those not ovulating by 14 days.

The responsiveness of the hypothalamo-pituitary axis to steroid treatments for ovarian synchronization and the ovarian superstimulatory response to exogenous FSH was compared in 13–14 year old cows and their 1–4 year old young daughters. We tested the hypotheses that aging in cattle is associated with: (1) decreased follicular wave synchrony after estradiol and progesterone treatment; (2) delayed LH surge and ovulation in response to exogenous preovulatory estradiol treatment; (3) reduced superstimulatory response to exogenous FSH. Higher plasma FSH concentrations ( P P = 0.07) for fewer 4–5 mm follicles at wave emergence were observed in old cows ( n = 10) than in young cows ( n = 9). The suppressive effect of estradiol/progesterone treatment on FSH was similar between old and young cows. Although the preovulatory LH surge in response to estradiol treatment was delayed in old than young cows ( P = 0.01), detected ovulation times were not different. No difference in ovarian superstimulatory response was detected between age groups, but old cows ( n = 8) tended ( P = 0.10) to have fewer large follicles (≥9 mm) 12 h after last FSH treatment than in young cows ( n = 7). We concluded that pituitary and ovarian responsiveness to estradiol/progesterone synchronization treatment was similar between old and young cows, but aging was associated with a delayed preovulatory LH surge subsequent to estradiol treatment. Old cows tended to have fewer large follicles after superstimulatory treatment than young cows.

Systemic and intratympanic steroids are most widely used for treating idiopathic sudden sensorineural hearing loss. Other treatments include vasodilator, immunosuppressant and antiviral medication. However, only 61% of patients achieve full recovery, and controversies about the standard treatment still exist. In this case report, we present a patient with idiopathic sudden sensorineural hearing loss who failed to respond to systemic and intratympanic steroid treatments but subsequently recovered after undergoing hyperbaric oxygen therapy.

To evaluate the effect of gonadal steroid treatment and thyroidectomy on concentrations of gonadotropins and thyroid-stimulating hormone in the bovine, nonlactating Holstein cows were either thyroidectomized and ovariectomized (THYOVEX; n = 6) or ovariectomized only (OVEX; n = 4), and subsequently treated with no gonadal steroids (control), estradiol-17 beta (E2), progesterone (P4), or P4+E2 in a 2 x 4 factorial experiment. Averaged across steroid treatments, baseline concentrations of luteinizing hormone (LH; P.05) and follicle-stimulating hormone (FSH; P.10) were higher in THYOVEX cows than in OVEX cows. Pulse frequencies and amplitudes of LH and FSH did not differ between THYOVEX and OVEX cows. Secretion of TSH was pulsatile and all concentrations and pulsatile characteristics of TSH were increased (P.05) in THYOVEX compared to OVEX cows. Treatment with E2 and P4 decreased (P.05) baseline concentrations and magnitude of LH pulses, whereas P4+E2 increased (P.01) pulse frequency of LH and FSH. Amplitude of LH and FSH pulses were not affected by treatment with either steroid. Treatment with P4+E2 decreased (P.05) baseline concentrations of TSH, whereas pulse frequency, and magnitude and amplitude of TSH pulses were not altered by treatment with steroids. Mean concentrations of LH and FSH were similar during 48 hr after termination of E2 and P4+E2 treatments, but concentrations of TSH were higher (P = .06) after P4+E2 than after E2. Secretion of TSH showed a diurnal variation, with the lowest concentrations in the morning and highest in the afternoon. These results indicate that thyroidectomy influenced secretion of gonadotropins in OVEX cows.

Ten cases are reported of polycystic ovary syndrome (PCOS) in association with psychiatric illness presenting to a liaison psychiatry service. This association is critically reviewed paying attention to explanatory factors such as selection bias and steroid treatments. Monoamine imbalances may be involved in the etiology of both PCOS and the accompanying psychiatric illness.

Sir—The parents of three different children with atopic eczema seen in our paediatric dermatology clinics informed us that they were applying a product called Wau Wa cream to their children’s skin, with substantial benefit. In every case, the parents had presumed that this product was free from corticosteroids, which they believed to be harmful. One child had skin atrophy at several sites. Wau Wa cream is widely available in the UK, especially in southeast England. Its label states that it contains extract of Wau Wa root and cream, and is made in Ghana. Independent analysis shows that Wau Wa cream contains 0·013% clobetasol propionate. This corticosteroid molecule is the same as that present in one of the most potent commercially available prescription topical corticosteroid treatments, although the concentration is about a quarter of that used in the commercial preparation, in which the concentration is 0·05%. The data sheet for the prescription cream states it must not be used long term in children. The Wau Wa tree grows in Ghana and, paradoxically, causes severe dermatitis in timber workers; no therapeutic use for it is known. Clobetasol propionate is a synthetic steroid molecule and does not occur naturally; therefore, it is highly improbable that it is derived from the root of the tree. Parents are using this Wau Wa cream as an alternative to steroid treatments, unaware that is it not purely a herbal product. Doctors, under the same misconception, have recommended it to patients. Anyone known to be applying it should be made aware that it contains a potent corticosteroid that could damage the skin under certain circumstances. The Department of Health has been informed of the illegal sale of this cream. There have been previous concerns about steroids in herbal creams from China and Ireland. The wide availability of this cream emphasises the need for improved quality control for all herbal products. Also, more effective controls of the entry into the UK of illegal drugs of all types is desirable. *Justin Daniels, Debbie Shaw, David Atherton

A certain plasticity of gonadal sex differentiation was reported in the 1930s following exogenous steroid treatments in fish, but demonstration that some environmental factors (temperature, pH, density and social interactions) can influence the sex ratio in gonochoristic species, is relatively recent. In fish, as in reptiles and amphibians displaying environmental sex determination the main environmental factor influencing sex seems to be temperature (TSD = Temperature Sex Determination). In most of the thermosensitive species (some Atherinids, Poecilids, Cichlids, the tilapias, the goldfish, a Siluriform, a flatfish,...) the male to female ratio increases with temperature, and/or ovarian differentiation is induced by low temperatures. Conversely, in some rare species (Dicentrarchus labrax, Ictalurus punctatus), high temperatures may produce female-biased sex ratios and/or low temperatures promote male-biased sex ratios. In the case of the hirame Paralichthys olivaceus, both high and low temperatures induce monosex inale populations while intermediate temperatures yield a 1 :I sex ratio (U-shape curve). Fish show particularities in their TSD patterns since monosex populations are generally not produced at extreme temperatures, suggesting the existence of strong temperature/genotype interactions. In reptiles, amphibians as well as fish displaying TSD, temperature treatments must be applied at a critical sensitive period which is relatively similar to the hormone-sensitive period. In gonochoristic fish, steroid hormones with estrogens in females and II-oxygenated androgens in males, are probably key physiological steps in the regulation of the gonadal sex differentiation. Cytochrome P450-aromatase, an enzyme which catalyses the conversion of androgens to estrogens, seems to be a critical enzyme for ovarian differentiation. The molecular mechanisms of thermosensitivity have been addressed in only two species. In both the tilapia, Oreochromis niloticus and the hirame, aromatase gene expression is down-regulated by masculinizing-temperature treatments. Furthermore, in tilapia the gene expression of II [bêta]-hydroxylase (a key enzyme involved in the synthesis of II-oxygenated androgens) does not appear to be affected by temperature treatments. (Texte intégral)

A female aged 44 diagnosed as having bilateral Meniere's disease was treated by various medications. While on a vasodilator, hearing ability remained unchanged. Furosemide and steroid treatments resulted in a good response. Hearing impairment in one ear is often accompanied by improvement in the contralateral ear. This phenomenon is one of the characteristics of bilateral Meniere's disease.

The interaction of estradiol and progesterone in controlling gonadotropin secretion was investigated in cyclic and anestrous ewes. The peak response of ewes to 200 ng of [D-Leu6, des-Gly NH210 proethylamide9]-GnRH, in terms of serum LH concentrations, was greater on days 7 and 15 of the cycle (65.6 ± 23.60 ng/ml and 72.1 ± 14.82 ng/ml) than on days 2 and 11 (33.1 ± 11.12 ng/ml and 27.7 ± 6.3 ng/ml) (P 0.05). Using blank silastic rubber implants (no steroid) and various sizes of implants containing estradiol, serum estradiol concentrations of 20.6 ± 2.8 pg/ml, 33.0 ± 1.9 pg/ml, 37.7 ± 1.6 pg/ml, or 48.4 ± 1.8 pg/ml were produced in 4 groups of mid cycle ewes (days 7–9). Three of 5 ewes exhibiting the highest estradiol levels experienced a transient peak in serum concentrations of LH and FSH 24 ± 6 hr after implant insertion (LH 19.1 ± 3.84 ng/ml, FSH 34.3 ± 11.13 ng/ml). These 3 ewes subsequently underwent luteolysis. Estradiol treatment at mid cycle enhanced the response to the GnRH analog (P

Experiments were conducted to assess the influence of the ovary and various steroid treatments on the development of the delayed anovulatory syndrome (DAS) in female rats. The influence of neonatally administered androgen on the development of ovarian function and female sexual behaviour was studied. It was found that neither the presence of the ovary nor the administration of oestrogen or androgen affected the time-course of the DAS. Doses of androgen which produced the DAS had little effect on female sexual behaviour and there was no evidence of time-dependent changes in sexual behaviour comparable to the time-dependent changes of ovarian physiology observed during the DAS.

The importance of lymphocytes in initiating various immunologic processes has been emphasized repeatedly (Gowans et al., 1961). This contention is well supported by past investigations which have shown that all treatments which reduce or abolish lymphocytes in experimental subjects, for instance irradiation, steroid treatments, thoracic duct drainage, etc., cause a serious impairment in their ability to respond to subsequent immunologic challenges. Furthermore, transfer studies have demonstrated the ability of lymphocytes from challenged animals to produce a response in immunologically incompetent recipients. Although conclusions drawn from such studies have to be interpreted with qualifications in terms of the identity of cell types involved, they nevertheless suggest the possibility that lymphocytes are capable of retaining certain antigens.