Safety and efficacy of melatonin supplementation as an add-on treatment for infantile epileptic spasms syndrome: A randomized, placebo-controlled, double-blind trial.

This was a prospective, randomized, double-blind, single-center placebo-controlled trial to assess the efficacy and safety of melatonin as an add-on treatment for infantile epileptic spasms syndrome (IESS). Participants aged 3 months to 2 years with a primary diagnosis of IESS were recruited and assigned to two groups in a 1:1 ratio. Both treatment groups received a combination of adrenocorticotrophic hormone (ACTH) and magnesium sulfate (MgSO4 ) for 2 weeks, and the treatment group also received melatonin (3 mg) between 20:00 and 21:00 daily, 0.5-1 h before bedtime. The study's primary endpoint was the average reduction rate in spasm frequency assessed by seizure diaries. Secondary endpoints included assessment of the response rate, EEG hypsarrhythmia (Kramer score), and psychomotor development (Denver Developmental Screening Test, DDST). Sleep quality was assessed by using the Brief Infant Sleep Questionnaire (BISQ), the Infant Sleep Assessment Scale (ISAS), and actigraphy. Safety parameters were also evaluated. Statistical analyses were conducted on intention-to-treat and per-protocol populations. The trial is registered at Clinicaltrials.gov (ChiCTR2000036208). Out of 119 screened patients, 70 were randomized and 66 completed treatments. In the intention-to-treat population, there were no significant differences in the average percentage reduction of spasm frequency (median [interquartile range, IQR: Q3-Q1], 100% [46.7%] vs. 66.7% [55.3%], p = .288), the 3-day response rate (51.4% vs. 37.1%, p = .229), the 28-day response rate (42.9% vs. 28.6%, p = .212), EEG Kramer scores (2 [3.5] vs. 2 [3], p = .853), or DDST comprehensive months (5 [2.5] vs. 6 [6], p = .239) between the melatonin (n = 35) and placebo (n = 35) groups. However, caregivers reported improved sleep quality after melatonin treatment, with 85.7% reporting regular sleep compared to 42.9% with placebo (42.9%, p < .001). The melatonin group had lower ISAS scores in 4-11-month-old patients compared to the placebo (mean ± SD, 29.3 ± 4.4 vs. 35.2 ± 5.9, p < .001). Moreover, the median (IQR) value of sleep-onset latency was shortened by 6.0 (24.5) min after melatonin treatment, while that in the placebo group was extended by 3.0 (22.0) min (p = .030). The serum melatonin (6:00 h) level (pg/mL) of the children in the melatonin group after treatment was significantly higher than in the placebo group (median [IQR], 84.8 [142] vs. 17.5 [37.6], p < .001). No adverse effects related to melatonin were observed in the study, and there were no significant differences in adverse effects between the melatonin and placebo groups. Although not statistically significant, the results of this randomized clinical trial proved that melatonin supplementation, as an add-on treatment, can improve spasm control rate in the treatment of IESS. For IESS children treated with ACTH, the addition of melatonin was found to improve sleep quality, shorten sleep onset latency, and increase blood melatonin levels. Moreover, it was observed to be a safe treatment option.

The ethanol extract of Periplaneta Americana L. improves ulcerative colitis induced by a combination of chronic stress and TNBS in rats.

PURPOSE: To investigate the effects of Periplaneta americana L. on ulcerative colitis (UC) induced by a combination of chronic stress (CS) and 2,4,6-trinitrobenzene sulfonic acid enema (TNBS) in rats. METHODS: The experiment UC model with CS was established in rats by a combination of chronic restraint stress, excess failure, improper, and TNBS. The body weight, disease activity index (DAI), colonic mucosal injury index (CMDI), histopathological score (HS) and pro-inflammatory mediators were measured. The content of corticotropin-releasing hormone (CRH) in hypothalamus or adrenocorticotropic hormone (ACTH) and corticosteroids (CORT) in plasma were evaluated by enzyme-linked immunosorbent assay. The proportion of T lymphocyte subsets was detected by flow cytometry, and gut microbiota was detected by 16S rDNA amplicon sequencing. RESULTS: Weight loss, DAI, CMDI, HS and proinflammatory mediators were reversed in rats by P. americana L. treatment after UC with CS. Increased epidermal growth factor (EGF) was observed in P. americana L. groups. In addition, P. americana L. could reduce the content of CRH and ACTH and regulate the ratio of CD3+, CD3+CD8+ and CD3+CD4+CD25+/CD4+ in spleen. Comparably, P. americana L. changes composition of gut microbiota. CONCLUSIONS: The ethanol extract of Periplaneta Americana L. improves UC induced by a combination of CS and TNBS in rats.

Efficacy and Safety of Vamorolone vs Placebo and Prednisone Among Boys With Duchenne Muscular Dystrophy: A Randomized Clinical Trial.

Importance: Corticosteroidal anti-inflammatory drugs are widely prescribed but long-term use shows adverse effects that detract from patient quality of life. Objective: To determine if vamorolone, a structurally unique dissociative steroidal anti-inflammatory drug, is able to retain efficacy while reducing safety concerns with use in Duchenne muscular dystrophy (DMD). Design, Setting, and Participants: Randomized, double-blind, placebo- and prednisone-controlled 24-week clinical trial, conducted from June 29, 2018, to February 24, 2021, with 24 weeks of follow-up. This was a multicenter study (33 referral centers in 11 countries) and included boys 4 to younger than 7 years of age with genetically confirmed DMD not previously treated with corticosteroids. Interventions: The study included 4 groups: placebo; prednisone, 0.75 mg/kg per day; vamorolone, 2 mg/kg per day; and vamorolone, 6 mg/kg per day. Main Outcomes and Measures: Study outcomes monitored (1) efficacy, which included motor outcomes (primary: time to stand from supine velocity in the vamorolone, 6 mg/kg per day, group vs placebo; secondary: time to stand from supine velocity [vamorolone, 2 mg/kg per day], 6-minute walk distance, time to run/walk 10 m [vamorolone, 2 and 6 mg/kg per day]; exploratory: NorthStar Ambulatory Assessment, time to climb 4 stairs) and (2) safety, which included growth, bone biomarkers, and a corticotropin (ACTH)-challenge test. Results: Among the 133 boys with DMD enrolled in the study (mean [SD] age, 5.4 [0.9] years), 121 were randomly assigned to treatment groups, and 114 completed the 24-week treatment period. The trial met the primary end point for change from baseline to week 24 time to stand velocity for vamorolone, 6 mg/kg per day (least-squares mean [SE] velocity, 0.05 [0.01] m/s vs placebo -0.01 [0.01] m/s; 95% CI, 0.02-0.10; P = .002) and the first 4 sequential secondary end points: time to stand velocity, vamorolone, 2 mg/kg per day, vs placebo; 6-minute walk test, vamorolone, 6 mg/kg per day, vs placebo; 6-minute walk test, vamorolone, 2 mg/kg per day, vs placebo; and time to run/walk 10 m velocity, vamorolone, 6 mg/kg per day, vs placebo. Height percentile declined in prednisone-treated (not vamorolone-treated) participants (change from baseline [SD]: prednisone, -1.88 [8.81] percentile vs vamorolone, 6 mg/kg per day, +3.86 [6.16] percentile; P = .02). Bone turnover markers declined with prednisone but not with vamorolone. Boys with DMD at baseline showed low ACTH-stimulated cortisol and high incidence of adrenal insufficiency. All 3 treatment groups led to increased adrenal insufficiency. Conclusions and Relevance: In this pivotal randomized clinical trial, vamorolone was shown to be effective and safe in the treatment of boys with DMD over a 24-week treatment period. Vamorolone may be a safer alternative than prednisone in this disease, in which long-term corticosteroid use is the standard of care. Trial Registration: ClinicalTrials.gov Identifier: NCT03439670.

Treatment of children with infantile spasms: A network meta-analysis.

AIM: We performed a systematic review and network meta-analysis (NMA) to obtain comparative effectiveness estimates and rankings of non-surgical interventions used to treat infantile spasms. METHOD: All randomized controlled trials (RCTs) including children 2 months to 3 years of age with infantile spasms (with hypsarrhythmia or hypsarrhythmia variants on electroencephalography) receiving appropriate first-line medical treatment were included. Electroclinical and clinical remissions within 1 month of starting treatment were analyzed. RESULTS: Twenty-two RCTs comparing first-line treatments for infantile spasms were reviewed; of these, 17 were included in the NMA. Both frequentist and Bayesian network rankings for electroclinical remission showed that high dose adrenocorticotropic hormone (ACTH), methylprednisolone, low dose ACTH and magnesium sulfate (MgSO4 ) combination, low dose ACTH, and high dose prednisolone were most likely to be the 'best' interventions, although these were not significantly different from each other. For clinical remission, low dose ACTH/MgSO4 combination, high dose ACTH (with/without vitamin B6 ), high dose prednisolone, and low dose ACTH were 'best'. INTERPRETATION: Treatments including ACTH and high dose prednisolone are more effective in achieving electroclinical and clinical remissions for infantile spasms. WHAT THIS PAPER ADDS: Adrenocorticotropic hormone and high dose prednisolone are more effective than other medications for infantile spasms. Symptomatic etiology decreases the likelihood of remission even after adjusting for treatment lag.

Randomized trial of high-dose pyridoxine in combination with standard hormonal therapy in West syndrome.

OBJECTIVE: To determine whether high-dose, oral pyridoxine in combination with standard adrenocorticotropic hormone (ACTH) therapy has superior effectiveness than ACTH therapy alone in increasing cessation of epileptic spasms for children with West syndrome. METHODS: This study was an open-label, randomized controlled trial with masked endpoint assessments. Eligible children with West syndrome, age ranged 3-18 months, were randomized into the intervention (n = 43) and the standard arm (n = 37) of therapy. The intervention group received oral pyridoxine at 100-300 mg/kg/day in addition to standard therapy of intramuscular ACTH at 150 IU/m2/day. Primary effectiveness outcome was a complete cessation of spasms at two weeks and sustained till six weeks. RESULTS: Comparison of effectiveness measures between intervention and standard groups were : complete cessation of epileptic spasms (48.8% vs 58.3%; group difference -9.6%; 95% confidence interval [CI] -30% to 12.3%; p = 0.4), median EEG scores (Q1-Q3) by Jeavons Score at six weeks [3 (1-5) vs 3 (1-5); p = 0.6], median motor scores (Q1-Q3) by DASII (Development Assessment Scales for Indian Infants) at 12 weeks [35 (29-49) vs 42 (34.3-63.8), p = 0.04], and median mental scores (Q1-Q3) by DASII at 12 weeks [35 (29.5-46) vs 41.5 (31.3-60), p = 0.02]. Adverse events were comparable in both arms. CONCLUSIONS: There was no evidence to suggest the superiority of high-dose pyridoxine in combination with ACTH versus ACTH alone for the treatment of West syndrome, considering the limitations of the study design.

Adrenocorticotropic hormone: an effective "natural" biologic therapy for acute gout?

Treatment of acute gout consists of non-steroidal anti-inflammatory drugs (NSAIDs), colchicine and steroids. However, the typical patient with gout has multiple comorbidities such as cardiovascular disease, hypertension, renal dysfunction or diabetes/metabolic syndrome that represent contraindications to these therapeutic options. The aim of this study is to review the available evidence regarding the use of ACTH as an alternative therapeutic option for acute gout and explore potential mechanisms of action. We performed an electronic search (MEDLINE, Scopus and Web of Science) using the keywords ACTH or adrenocorticotropic hormone combined with gout or crystal-induced arthritis. ACTH appears suitable for patients with many comorbidities due to its good safety profile. Clinical evidence shows that ACTH is at least as effective as classic agents. The mechanism of action of ACTH in gout is not entirely known. Robust experimental evidence points to the direction that ACTH does not act solely by triggering the release of endogenous steroids but also appears to downregulate inflammatory responses by activating melanocortin receptors on innate immune cells, such as macrophages. Moreover, indirect evidence indicates that ACTH may have an IL-1 antagonistic effect. We propose that ACTH may be an alternative therapeutic option for gout in patients with multiple comorbidities. Large-scale studies assessing the efficacy and safety of ACTH compared to classic therapeutic options are needed.

The Role of Hormones and Trophic Factors as Components of Preservation Solutions in Protection of Renal Function before Transplantation: A Review of the Literature.

Transplantation is currently a routine method for treating end-stage organ failure. In recent years, there has been some progress in the development of an optimal composition of organ preservation solutions, improving the vital functions of the organ and allowing to extend its storage period until implantation into the recipient. Optimizations are mostly based on commercial solutions, routinely used to store grafts intended for transplantation. The paper reviews hormones with a potential nephroprotective effect, which were used to modify the composition of renal perfusion and preservation solutions. Their effectiveness as ingredients of preservation solutions was analysed based on a literature review. Hormones and trophic factors are innovative preservation solution supplements. They have a pleiotropic effect and affect normal renal function. The expression of receptors for melatonin, prolactin, thyrotropin, corticotropin, prostaglandin E1 and trophic factors was confirmed in the kidneys, which suggests that they are a promising therapeutic target for renal IR (ischemia-reperfusion) injury. They can have anti-inflammatory, antioxidant and anti-apoptotic effects, limiting IR injury.

Drug therapy for treating post-dural puncture headache.

BACKGROUND: This is an updated version of the original Cochrane review published in Issue 8, 2011, on 'Drug therapy for treating post-dural puncture headache'.Post-dural puncture headache (PDPH) is the most common complication of lumbar puncture, an invasive procedure frequently performed in the emergency room. Numerous pharmaceutical drugs have been proposed to treat PDPH but there are still some uncertainties about their clinical effectiveness. OBJECTIVES: To assess the effectiveness and safety of drugs for treating PDPH in adults and children. SEARCH METHODS: The searches included the Cochrane Central Register of Controlled Trials (CENTRAL 2014, Issue 6), MEDLINE and MEDLINE in Process (from 1950 to 29 July 2014), EMBASE (from 1980 to 29 July 2014) and CINAHL (from 1982 to July 2014). There were no language restrictions. SELECTION CRITERIA: We considered randomised controlled trials (RCTs) assessing the effectiveness of any pharmacological drug used for treating PDPH. Outcome measures considered for this review were: PDPH persistence of any severity at follow-up (primary outcome), daily activity limited by headache, conservative supplementary therapeutic option offered, epidural blood patch performed, change in pain severity scores, improvements in pain severity scores, number of days participants stay in hospital, any possible adverse events and missing data. DATA COLLECTION AND ANALYSIS: Review authors independently selected studies, assessed risk of bias and extracted data. We estimated risk ratios (RR) for dichotomous data and mean differences (MD) for continuous outcomes. We calculated a 95% confidence interval (CI) for each RR and MD. We did not undertake meta-analysis because the included studies assessed different sorts of drugs or different outcomes. We performed an intention-to-treat (ITT) analysis. MAIN RESULTS: We included 13 small RCTs (479 participants) in this review (at least 274 participants were women, with 118 parturients after a lumbar puncture for regional anaesthesia). In the original version of this Cochrane review, only seven small RCTs (200 participants) were included. Pharmacological drugs assessed were oral and intravenous caffeine, subcutaneous sumatriptan, oral gabapentin, oral pregabalin, oral theophylline, intravenous hydrocortisone, intravenous cosyntropin and intramuscular adrenocorticotropic hormone (ACTH).Two RCTs reported data for PDPH persistence of any severity at follow-up (primary outcome). Caffeine reduced the number of participants with PDPH at one to two hours when compared to placebo. Treatment with caffeine also decreased the need for a conservative supplementary therapeutic option.Treatment with gabapentin resulted in better visual analogue scale (VAS) scores after one, two, three and four days when compared with placebo and also when compared with ergotamine plus caffeine at two, three and four days. Treatment with hydrocortisone plus conventional treatment showed better VAS scores at six, 24 and 48 hours when compared with conventional treatment alone and also when compared with placebo. Treatment with theophylline showed better VAS scores compared with acetaminophen at two, six and 12 hours and also compared with conservative treatment at eight, 16 and 24 hours. Theophylline also showed a lower mean "sum of pain" when compared with placebo. Sumatriptan and ACTH did not show any relevant effect for this outcome.Theophylline resulted in a higher proportion of participants reporting an improvement in pain scores when compared with conservative treatment.There were no clinically significant drug adverse events.The rest of the outcomes were not reported by the included RCTs or did not show any relevant effect. AUTHORS' CONCLUSIONS: None of the new included studies have provided additional information to change the conclusions of the last published version of the original Cochrane review. Caffeine has shown effectiveness for treating PDPH, decreasing the proportion of participants with PDPH persistence and those requiring supplementary interventions, when compared with placebo. Gabapentin, hydrocortisone and theophylline have been shown to decrease pain severity scores. Theophylline has also been shown to increase the proportion of participants that report an improvement in pain scores when compared with conventional treatment.There is a lack of conclusive evidence for the other drugs assessed (sumatriptan, adrenocorticotropic hormone, pregabalin and cosyntropin).These conclusions should be interpreted with caution, due to the lack of information to allow correct appraisal of risk of bias, the small sample sizes of the studies and also their limited generalisability, as nearly half of the participants were postpartum women in their 30s.

Predictive value of EEG findings at control of epileptic spasms for seizure relapse in patients with West syndrome.

PURPOSE: To evaluate the prognostic importance of electroencephalography (EEG) findings at cessation of epileptic spasms for seizure outcome. METHODS: We reviewed 71 children with West syndrome (cryptogenic 14) who had obtained control of epileptic spasms with initial treatment (adrenocorticotropic hormone (ACTH) 37, high-dose vitamin B6 2, and antiepileptic drugs 32). According to the EEG findings at control of epileptic spasms, the subjects were divided into three groups: normal group (no epileptic activity, n=12), abnormal group (residual epileptic activity without hypsarrhythmia, n=53), and hypsarrhythmic group (persisting hypsarrhythmia, n=6). RESULTS: Overall, 47 (66%) of the 71 patients (cryptogenic 4) had experienced relapses of seizures (epileptic spasms 23 and focal seizure 24) after initial control of epileptic spasms. Within symptomatic cases, seizure relapse rate varied widely from 0% (Down syndrome) to 100% (tuberous sclerosis), depending on underlying causes. Seizure relapse depended on the EEG findings at control of epileptic spasms. The normal group had a significantly lower seizure relapse rate (17%) in comparison with the abnormal group (75%), the hypsarrhythmic group (83%), and the epileptiform (abnormal plus hypsarrhythmic, 76%) group. No significant difference in seizure relapse rate was observed between non-hypsarrhythmic (normal plus abnormal, 65%) and hypsarrhythmic groups. At the last follow-up, normal group children also showed a favorable seizure prognosis (seizure control 100%). CONCLUSIONS: A favorable seizure prognosis is associated with the disappearance of epileptic activity, but not the resolution of hypsarrhythmic pattern on EEG at control of epileptic spasms. We suggest that effective treatment for West syndrome should produce both cessation of epileptic spasms and disappearance of epileptic activity on EEG.

Treatment of idiopathic membranous nephropathy.

Immunosuppressive treatment of patients with idiopathic membranous nephropathy (iMN) is heavily debated. The controversy is mainly related to the toxicity of the therapy and the variable natural course of the disease-spontaneous remission occurs in 40-50% of patients. The 2012 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for Glomerulonephritis provides guidance for the treatment of iMN. The guideline suggests that immunosuppressive therapy should be restricted to patients with nephrotic syndrome and persistent proteinuria, deteriorating renal function or severe symptoms. Alkylating agents are the preferred therapy because of their proven efficacy in preventing end-stage renal disease. Calcineurin inhibitors can be used as an alternative although efficacy data on hard renal end points are limited. In this Review, we summarize the KDIGO guideline and address remaining areas of uncertainty. Better risk prediction is needed to identify patients who will benefit from immunosuppressive therapy, and the optimal timing and duration of this therapy is unknown because most of the randomized controlled trials were performed in low-risk or medium-risk patients. Alternative therapies, directed at B cells, are under study. The discovery of anti-M type phospholipase A2 receptor-antibodies is a major breakthrough and we envisage that in the near future, antibody-driven therapy will enable more individualized treatment of patients with iMN.

Strategies for managing ACTH dependent mineralocorticoid excess induced by abiraterone.

BACKGROUND: Abiraterone strongly inhibits androgen synthesis but may lead to an increase in mineralocorticoid hormones that may impair its long term tolerability in patients with prostate cancer. How to implement available therapies in the management and prevention of these potential side effects is a matter of current clinical research. METHODS: The acute and long term consequences of mineralocorticoid excess and the effects of available treatments have been reviewed. Prospective studies in which abiraterone was employed were identified to assess the frequency and severity of the mineralocorticoid excess syndrome and the efficacy of ameliorating therapeutic approaches. RESULTS: Glucocorticoids to inhibit the ACTH increase that drives mineralocorticoid synthesis and mineralocorticoid receptor (MR) antagonists can be used in the management of the abiraterone-induced mineralocorticoid excess syndrome. Phase I and II trials of abiraterone without additional therapies revealed that mineralocorticoid excess symptoms occur in the majority of patients. Eplerenone, a specific MR antagonist, seems to be effective but it does not control the mineralocorticoid excess. Glucorticoid supplementation to control ACTH drive is therefore needed. In several randomized trials the addition of prednisone (10mg daily) to abiraterone was not able to prevent mineralocorticoid excess syndrome in many cases and thus cannot be considered the gold standard. CONCLUSION: At present, the best conceivable treatment for managing the abiraterone-induced mineralocorticoid excess consists of the administration of glucocorticoid replacement at the lowest effective dose ± MR antagonists and salt deprivation. The drug doses should be modulated by monitoring blood pressure, fluid retention and potassium levels during therapy.

Molecular testing in congenital adrenal hyperplasia due to 21α-hydroxylase deficiency in the era of newborn screening.

Newborn screening (NBS) identifies the majority of classical [salt-wasting (SW) and simple-virilizing (SV)] cases of congenital adrenal hyperplasia (CAH) due to 21α-hydroxylase (21α-OHase) during the first days of life. Diagnosis of classical CAH is confirmed by follow-up serum 17-hydroxyprogesterone and/or the adrenocorticotropin stimulation test; however, neither test definitively distinguishes between the classical subtypes. After confirmation, all newborns are started on hydrocortisone (glucocorticoid) and fludrocortisone (mineralocorticoid) treatment. While initiating fludrocortisone treatment in classical CAH patients, independent of subtype and before SW signs or symptoms occur, prevents a life-threatening SW crisis, it may later complicate distinguishing between the classical subtypes. Genotype-phenotype correlations in 21α-OHase deficiency are excellent; however, molecular testing is not a regular part of the diagnostic workup. Molecular testing on 39 patients (25 identified by NBS) with an already established diagnosis of CAH identified 11 SW patients (8 identified by NBS) whose mutations suggested further biochemical and clinical reassessment of their subtype. Overall, SW accounted for 57.6% of our classical CAH patients, below the generally accepted figure that >75% of classical CAH are comprised of the SW form. In the era of NBS, molecular testing is a valuable supplemental tool identifying patients who may benefit from reassessment of their salt-retaining ability.

Drug therapy for treating post-dural puncture headache.

BACKGROUND: Post-dural puncture headache (PDPH) is the most common complication of lumbar puncture, an invasive procedure frequently performed in the emergency room. Numerous pharmaceutical drugs have been proposed to treat PDPH but there are still some uncertainties about their clinical effectiveness. OBJECTIVES: To assess the effectiveness and safety of drugs for treating PDPH in adults and children. SEARCH STRATEGY: The search strategy included the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (2011, Issue 2), MEDLINE (from 1950 to June 2011), EMBASE (from 1980 to June 2011) and CINAHL (from 1982 to June 2011). There was no language restriction. SELECTION CRITERIA: We considered randomised controlled trials (RCTs) assessing the effectiveness of any pharmacological drug used for treating PDPH. DATA COLLECTION AND ANALYSIS: Review authors independently selected studies, assessed risks of bias and extracted data. We estimated risk ratios (RR) for dichotomous data and mean differences (MD) for continuous outcomes. We calculated a 95% confidence interval (CI) for each RR and MD. We did not undertake meta-analysis because the included studies assessed different sorts of drugs or different outcomes. We performed an intention-to-treat (ITT) analysis. MAIN RESULTS: We included seven RCTs (200 participants) in this review (between 88% and 90.5% were women; mostly parturients (84% to 87%) after a lumbar puncture for a regional anaesthesia). Pharmacological drugs assessed were oral and intravenous caffeine, subcutaneous sumatriptan, oral gabapentin, oral theophylline, intravenous hydrocortisone and intramuscular adrenocorticotropic hormone (ACTH).One RCT reported data about PDPH persistence of any severity at follow up (primary outcome); caffeine reduced the number of participants with PDPH at one to two hours when compared to placebo. Treatment with caffeine also decreased the need for a conservative supplementary therapeutic option. Treatment with gabapentin versus placebo reported better visual analogue scale (VAS) scores after one, two, three and four days; treatment with hydrocortisone plus conventional treatment showed better VAS scores than conventional treatment alone at six, 24 and 48 hours and treatment with theophylline showed a lower mean "sum of pain" when compared with placebo. Sumatriptan and ACTH did not show any relevant effect for this outcome.There were no clinically significant drug adverse events.The rest of the outcomes were not reported by the RCTs or did not show any relevant effect. AUTHORS' CONCLUSIONS: Caffeine has shown effectiveness for treating PDPH, decreasing the proportion of participants with PDPH persistence and those requiring supplementary interventions, when compared with placebo. Gabapentin, theophylline and hydrocortisone have also shown a decrease in pain severity scores when compared with placebo or conventional care.There is a lack of conclusive evidence for the other drugs assessed (sumatriptan and ACTH).These conclusions should be interpreted with caution, due to the lack of information to allow correct appraisal of risk of bias, the small sample sizes of studies and also the limited generalisability, as most participants were post-partum women in their 30s.

A case of human intramuscular adrenal gland transplantation as a cure for chronic adrenal insufficiency.

Intramuscular endocrine gland transplantation has been well described as it pertains to parathyroid autotransplantation; however, transplantation of the adrenal gland is less well characterized. While adrenal autotransplantation in the setting of Cushing's disease has been described, intramuscular adrenal allotransplantation as a cure for adrenal insufficiency to our knowledge has not been previously carried out. Current treatment for adrenal insufficiency leaves patients without diurnal variation in cortisol release and susceptible to the detrimental effects of chronic hypercortisolism. We describe here the case of a 5-year-old girl with renal failure who had adrenal insufficiency following fulminant meningococcemia that led to requirements for both stress-dose steroid and mineralocorticoid replacement. Ten months after the onset of her disease, she received a simultaneous renal and adrenal gland transplant from her mother. The adrenal gland allograft was morselized into 1 mm(3) segments and implanted into three 2 cm pockets created in her rectus abdominis muscle. Three years after surgery, her allograft remains fully functional, responding well to adrenocorticotropin hormone stimulation and the patient does not require any steroid or mineral-corticoid supplementation. We believe this case represents the first description of successful functional intramuscular adrenal allograft transplantation with long-term follow up as a cure for adrenal insufficiency.

Positron emission tomography with glucose hypermetabolism of a hypothalamic hamartoma in infantile spasms associated with Pallister-Hall syndrome.

Although hypothalamic hamartomas (HHs) have been shown to be intrinsically epileptogenic and to participate in the generation of gelastic seizures, no evidence has been reported regarding its contribution to the pathogenesis of infantile spasms. We describe a male infant with Pallister-Hall syndrome who had a large HH presenting with infantile spasms without hypsarrhythmia. [(18)F]fluoro-deoxyglucose positron emission tomography scan performed during the period of epileptic spasms demonstrated glucose hypermetabolism of the HH, which resolved after cessation of the spasms with adrenocorticotropin hormone treatment. No concurrent increased metabolic activity in the lenticular nuclei or brainstem was observed in the ictal or interictal states. The present case suggests that HHs may be involved in the pathogenesis of infantile spasms, possibly with propagation of epileptic discharges from the hamartoma to the descending spinal pathway.

Gout--what are the treatment options?

There has been an increase in the incidence and prevalence of gout in the past several decades. A distinction needs to be made between the treatment of gout as an acute inflammatory disease and the lowering of the serum urate (SU) levels into a normal range. Treating acute gout attacks alone is not sufficient to prevent the disease from progressing. When treating gout one needs to treat acute attacks, and lower excess stores of uric acid to achieve dissolution of monosodium urate crystals through a long-term reduction of SU concentrations far beyond the threshold for saturation of urate and provide prophylaxis to prevent acute flares. The options available for the treatment of acute gout are NSAIDs, colchicine, corticosteroids, adrenocorticotropic hormone (ACTH) and intra-articular corticosteroids. The most important determinant of therapeutic success is not which anti-inflammatory agent is chosen, but rather how soon therapy is initiated and that the dose be appropriate. Prophylaxis should be considered an adjunct, rather than an alternative, to long-term urate-lowering therapy. For purposes of maintaining patient adherence to urate-lowering therapy, there is interest in improving prophylaxis of such treatment-induced attacks. The optimal agent, dose and duration for gout prophylaxis are unknown and require further investigation. The importance of long-term management of gout is the reduction and maintenance of SU in a goal range, usually defined as less than 6.0 mg/dL. Allopurinol and benzbromarone remain the cornerstone drugs for reducing SU levels lower than the saturation threshold to dissolve urate deposits effectively. Febuxostat and pegloticase help to optimize control of SU levels, especially in those patients with the most severe gout. Other agents, such as fenofibrate and losartan may be helpful as adjuvant drugs. Treatment for gout has advanced little in the last 40 years, until recently. The recent development of new therapeutic options promises to provide much needed alternatives for the many patients with gout who are intolerant of or refractory to available therapies. It is important to note that inappropriate use of medications as opposed to an apparent refractoriness to available therapies is not uncommon.

Neurometabolic effects of ACTH on free amino compounds in opsoclonus-myoclonus syndrome.

To evaluate the possible role of central free amino compounds in pediatric opsoclonus-myoclonus syndrome (OMS), 21 cerebrospinal fluid (CSF) amino compounds were measured by an amino acid analyzer or mass spectroscopy in 74 anesthetized children, 54 with OMS and 20 age-matched neurological controls. In OMS, only phosphoethanolamine was increased compared to controls; OMS severity and duration had significant converse effects on alanine and phosphoethanolamine. In contrast, corticotropin (ACTH) treatment was associated with increased alanine and phenylalanine, and decreased taurine compared to controls and untreated OMS, and increased glutamine, lysine, ornithine, and tyrosine compared to untreated OMS. Other than low taurine, these effects were not found with corticosteroid treatment, and non-steroidogenic immunotherapy had no effect. The ACTH dose-association was most apparent for alanine and phosphoethanolamine, but lysine and ornithine were also higher in the high-dose ACTH group. There were no significant disease- or treatment-associated perturbations in GABA, glycine, or other amino acids. These data suggest a unique pattern of ACTH effects on non-neurotransmitter CSF amino compounds, for the most part not shared by steroids.

Update on the management of hyperuricemia and gout.

Gout is the most common inflammatory arthritis in the United States, with more than three million sufferers. Management of gout has changed relatively little in the past 50 years, despite the fact that many gout patients have contraindications to one or more currently available gout therapies. However, recent insights into gout pathophysiology suggest that time is ripe for a change. This article reviews recent updates in the management of gout, including new insights into dietary management that may permit better control of hyuperuricemia. Also reviewed are the biological and clinical data behind newly-developed drugs for gout that are likely to receive serious consideration for FDA approval, and clinical use, in the foreseeable future.

Audiogenic epilepsy in young mice of different strains after neonatal semax treatment.

Neonatal (from day 2 to day 7 of life) injection of neuropeptide semax to mice of 5 inbred strains significantly reduced predisposition to audiogenic epilepsy in only one-month-old DBA/2J mice, which manifested in changes in the mean audiogenic sensitivity score and percentage of animals dead as a result of acoustic stimulation.

Cushing's disease: a new approach to therapy in equine and canine patients.

Forty-one cases of Cushing's Disease affecting both equine and canine patients were treated with an identical mixture of two homeopathically prepared remedies (ACTH 30c and Quercus robur 30c), and the clinical improvements seen in the cases assessed. Homeopathy has been described as a medicine that can only be prescribed on the basis of individual symptoms shown, fitting the remedy to the patient, not the disease. The aim of this study was to define whether a standardised approach, using homeopathically prepared remedies, was a valid system of therapy for this disease, and if so, whether results were repeatable between species. The overall success rate for the therapy was 80% and results were broadly similar between the two species, indicating that homeopathy lends itself to the treatment of Cushing's Disease, and also to both cohort studies and group medicine.