Safety of phosphatidylserine containing omega3 fatty acids in ADHD children: a double-blind placebo-controlled trial followed by an open-label extension.

OBJECTIVE: To evaluate the safety of phosphatidylserine (PS) enriched with omega3 fatty acids, mainly eicosapentaenoic (PS-Omega3) in children with attention-deficit hyperactivity disorder (ADHD). METHODS: Two hundred children diagnosed with ADHD were randomised to receive either PS-Omega3 (300mg PS-Omega3/day) or placebo for 15 weeks. One hundred and fifty children continued into an open-label extension for an additional 15 weeks in which they all consumed PS-Omega3 (150mg PS-Omega3/day). Standard blood biochemical and haematological safety parameters, blood pressure, heart rate, weight and height were evaluated. Adverse events and the Side Effect Rating Scale were also assessed. RESULTS: One hundred and sixty-two participants completed the double-blind phase. No significant differences were noted between the two study groups in any of the safety parameters evaluated. One hundred and forty participants completed the open-label phase. At the end of this phase, no significant changes from baseline were observed in any of the studied parameters among participants who consumed PS-Omega3 for 30 weeks. CONCLUSIONS: Study results demonstrate that consumption of PS-Omega3 by children with ADHD, as indicated in a 30-week evaluation period, is safe and well tolerated, without any negative effect on body weight or growth.

The effect of phosphatidylserine containing Omega3 fatty-acids on attention-deficit hyperactivity disorder symptoms in children: a double-blind placebo-controlled trial, followed by an open-label extension.

OBJECTIVE: To study the efficacy and safety of phosphatidylserine (PS) containing Omega3 long-chain polyunsaturated fatty acids attached to its backbone (PS-Omega3) in reducing attention-deficit/ hyperactivity disorder (ADHD) symptoms in children. METHOD: A 15-week, double-blind, placebo-controlled phase followed by an open-label extension of additional 15 weeks. Two hundred ADHD children were randomized to receive either PS-Omega3 or placebo, out of them, 150 children continued into the extension. Efficacy was assessed using Conners' parent and teacher rating scales (CRS-P,T), Strengths and Difficulties Questionnaire (SDQ), and Child Health Questionnaire (CHQ). Safety evaluation included adverse events monitoring. RESULTS: The key finding of the double-blind phase was the significant reduction in the Global:Restless/impulsive subscale of CRS-P and the significant improvement in Parent impact-emotional (PE) subscale of the CHQ, both in the PS-Omega3 group. Exploratory subgroup analysis of children with a more pronounced hyperactive/impulsive behavior, as well as mood and behavior-dysregulation, revealed a significant reduction in the ADHD-Index and hyperactive components. Data from the open-label extension indicated sustained efficacy for children who continued to receive PS-Omega3. Children that switched to PS-Omega3 treatment from placebo showed a significant reduction in subscales scores of both CRS-P and the CRS-T, as compare to baseline scores. The treatment was well tolerated. CONCLUSIONS: The results of this 30-week study suggest that PS-Omega3 may reduce ADHD symptoms in children. Preliminary analysis suggests that this treatment may be especially effective in a subgroup of hyperactive-impulsive, emotionally and behaviorally-dysregulated ADHD children.

Trends in prescribing of psychotropic medications for inpatient adolescents in Israel: a 10 years retrospective analysis.

We examined the trends in prescribing psychotropic drugs to children and adolescents within an inpatients adolescent psychiatric ward in Israel. Data of 414 subjects, ranging from 12- to 22-year-old, covering the years 1997, 2002 and 2007, was examined retrospectively. Analyzed variables included the number and type of drug prescriptions per patient at discharge, the subjects' age at discharge and the number of diagnoses per patient at discharge. Analysis of variance (ANOVA) with repeated measures was used to evaluate changes between the three calendar years, along the 10-year study period, while Pearson χ(2) test was performed for categorical variables. Over the study period the mean age at discharge decreased significantly, by about a year and a half, the mean number of diagnoses increased significantly, from 1.6 to 2.4 diagnoses per patient and the total number of drugs prescribed at discharge increased significantly from 1.48 to 1.93 per patient. Overall, the number of patients who were prescribed mood stabilizers increased by 14%, those who were prescribed antidepressants increased by almost 24%, almost 16% in antipsychotics prescriptions and 51.5% in prescriptions of atypical antipsychotics. Typical antipsychotic prescriptions decreased by 35.5% and accordingly, the number of patients who were prescribed agents for the treatment of extra-pyramidal side effects decreased by almost 24%. Due to a low number of inpatients with attention deficit and hyperactivity disorder (ADHD), no significant statistical conclusion could be drawn regarding trends in psychostimulant prescriptions. Our findings agree with other published studies from the last two decades. The growing use of psychotropic agents in children and adolescents merit a continuous concern with regard to their effects on the developing brain and impact on quality of life and to authorizing these drugs for use in specific young age subgroups.

Radiographic imaging techniques for the diagnosis of abnormal uterine bleeding.

The introduction of SIS has been a significant advance in TVUS evaluation of the endometrial cavity in the 1990s. SIS provides an unparalleled, clear, enhanced view of the endomyometrial complex that cannot be obtained with TVUS alone. Focal and global endometrial pathology can be differentiated with SIS. Saline infusion improves the sensitivity for the detection of endometrial abnormalities. The continuing challenge for gynecologists is to provide patients with cost-effective, minimally invasive evaluation and directed therapy for menstrual dysfunction. SIS targets patients needing biopsy, directs the surgical approach, and minimizes office diagnostic hysteroscopy--all with a quick office procedure. For patients, the benefits include minimal and brief discomfort and a better understanding of intrauterine pathology through viewing the ultrasound monitor. Patients also appreciate the ease of scheduling, the minimal time away from work, and that no escort is needed after the procedure. SIS provides an extension of the pelvic gynecologic examination. SIS is the most important imaging modality for evaluating endometrial pathology. Although there is no perfect test to evaluate the endometrium, overall, SIS is superior to other imaging and diagnostic procedures. It is less expensive than D&C or hysteroscopy. It is a safe, efficient, convenient, and well-tolerated procedure. In some instances, however, neither TVUS nor SIS is definitive in determining the location of fibroids or able to discern adenomyosis. In these instances, MR imaging triage is helpful. MR imaging is gaining widespread acceptance and, in many instances, is a cost-effective tool in the evaluation of abnormal uterine bleeding. It is noninvasive, differentiates uterine anatomy in response to exogenous hormones or the normal menstrual cycle, and reliably localizes pelvic pathology and size of lesions. When uterine conservation is desired in women with fibroids and TVUS or SIS is indeterminate in localizing depth of myometrial involvement of a fibroid, MR imaging should be considered as a part of the clinical algorithm. The precision of MR imaging localization of submucosal fibroids can obviate the need for hysterectomy and permit a skilled surgeon to hysteroscopically resect the fibroids. If the clinical examination is suspicious for adenomyosis and the US is nondiagnostic, the clinician should consider MR imaging strongly. When the results of the imaging study would influence surgical route and planning, MR imaging should be considered in the preoperative evaluation.

Enema-induced perforation of the rectum in chronically constipated patients.

INTRODUCTION: The use of retrograde irrigation enemas is common in the treatment of chronic constipation, especially in the elderly. Perforation of the rectum and sigmoid colon caused by cleansing enemas, used by chronically constipated patients, has not been previously described. METHODS: We reviewed all patients with colorectal perforations caused by irrigation enemas admitted to our service in the three-year period between January 1995 and December 1997. RESULTS: Thirteen patients were treated by our surgical service because of perforations of the rectum and sigmoid colon related to a previous retrograde irrigation enema. Ten of these patients came from nursing homes, and the other three lived at home. The relevant information relating the enema administration to the patient's condition was given in only two of the ten patients referred to the emergency room by the institution's nursing or medical staff. In the other eight the information was vague and sometimes misleading. The diagnosis of colorectal perforation was made by history, plain abdominal x-rays, and CT scan with or without meglumine diatrizoate enemas. Ten patients survived, regardless of age, previous diseases, or operative findings. In all of them, diagnosis was made within 36 hours from the perforation. The three deaths occurred in patients in whom the diagnosis was made late. CONCLUSIONS: Awareness of the possible injury from enemas administered to chronically constipated patients should be stressed. A high degree of suspicion by the attending physician is extremely important, because prompt diagnosis and early surgical treatment carries a relatively good prognosis.

Effect of insulin-induced hypoglycemia on cytoskeleton-bound and cytosolic phosphofructokinase and the levels of glucose 1,6-bisphosphate in rat brain.

We investigated the regulatory mechanisms which may account for the reduction of glycolysis in brain during severe hypoglycemia. Phosphofructokinase (PFK), the rate-limiting enzyme in glycolysis, is known to be regulated by allosteric effectors, as well as by a reversible binding to cell cytoskeleton. These two mechanisms were studied, in rat brain, during insulin-induced hypoglycemia. Our experiments revealed that the intracellular distribution of PFK was not changed during severe hypoglycemia. However, the allosteric activity of the enzyme (assayed under conditions in which it is sensitive to allosteric effectors) from both the cytosolic (soluble) and cytoskeletal fractions, was significantly reduced. This reduction may be attributed to the marked fall in the level of glucose 1,6-bisphosphate (Glc-1,6-P2), the potent allosteric activator of PFK, as well as to the more moderate decrease in fructose 2,6-bisphosphate and the decrease in fructose 1,6-bisphosphate (the product and allosteric activator of the enzyme). In contrast to our previous findings in muscle, the cytoskeleton-bound PFK from brain was found to be sensitive to allosteric effectors like the soluble enzyme. This may explain the reduction in the allosteric activity of PFK in both the cytosolic and cytoskeletal fractions from brain. The decline in cytoskeleton-bound and cytosolic PFK activity, induced by the fall in its allosteric activators, may lead to the reduction in brain glycolytic rate, which was reflected by the marked decrease in lactate content during hypoglycemia.

Imaging variants of the liver, pancreas, and spleen.

The liver, spleen, and pancreas are three of the most frequently imaged intra-abdominal organs. Each organ is a complex structure affected by multiple pathologic processes. However, in order to recognize the pathologic changes that affect each organ, one must have a detailed knowledge of the broad spectrum of normal variants that can be seen when imaging the upper abdomen. This review explores the wide variability in appearance of the normal liver, spleen, and pancreas during cross-sectional imaging (CT, US, and MRI), stressing a thorough understanding of normal anatomy and the affect of physiologic variants.

Vaginal and vulvar adenosis. An unsuspected side effect of CO2 laser vaporization.

During a 15-month period, September 1984 through January 1986, 10 women who were treated in the Section of Gynecologic Oncology, Department of Obstetrics and Gynecology, Pennsylvania Hospital, Philadelphia, Pennsylvania, developed vaginal or vulvar adenosis after CO2 laser vaporization. The indications for therapy were condylomata of the cervix, vagina and vulva refractory to conservative management in 3 patients, vulvar intraepithelial neoplasia in 3, lichen sclerosus in 1 and cervical intraepithelial neoplasia with condylomata on the cervix and vagina in 3. All the patients underwent treatment of the vagina. Most underwent treatment of the cervix, and some underwent treatment of the vulva at various degrees of intensity and depth. During the posttreatment colposcopic follow-up examination, all the patients demonstrated lesions colposcopically consistent with adenosis of the vagina or vulva within the area treated with the CO2 laser. Biopsies of the lesions were performed, adenosis was confirmed histologically, and endometriosis was ruled out histologically. This entity has not been previously associated with CO2 laser vaporization, and its clinical significance is undetermined. Further follow-up is indicated.

Glucocorticoid and progesterone receptors in yolk sac placenta.

The parietal yolk sac (PYS) of the rat fetus at the 14th day of gestation contains glucocorticoid as well as progesterone receptors; both are present in the trophoblast cell layer. Following heat activation the receptors are capable of binding to deoxyribonucleic acid- (DNA-)cellulose. Glucocorticoid receptors, but not progesterone receptors, are also present in the visceral yolk sac (VYS) at the 14th day of gestation. Greater amounts (some 250 femtomoles/mg cytosol protein) of a glucocorticoid receptor are present in the VYS on the 17th day of gestation. The Kd is approximately 4 X 10(-9) M; following activation it also binds to DNA-cellulose. The elution pattern of the activated VYS receptor from diethylaminoethyl-(DEAE-)Sephadex, however, is similar to that found with kidney and colon rather than that of liver (i.e., it resembles corticosteroid binder IB rather than binder II) indicating a possible role in transport. Although the receptors are separate entities, progesterone competes as effectively as corticosterone for binding to the glucocorticoid receptors in both the PYS and and VYS, thus raising the question of the possible effect of changes in progesterone concentrations on the functioning of glucocorticoids during development.

Effect of atenolol treatment on urinary prostaglandins E2 and F2 alpha in essential hypertension.

The urinary excretion of prostaglandins (PG) E2 and F2 alpha was measured by radioimmunoassay in 15 patients with essential hypertension, before and after 2 and 4 weeks of treatment with the selective beta 1-adrenergic blocker, atenolol. Systolic and diastolic blood pressure, pulse rate and plasma renin activity decreased significantly during the treatment. No change was observed in renal function and electrolyte balance. The 24-hour excretion of PGE2 and PGF2 alpha was also unaffected by the antihypertensive treatment. The above findings, in contrast with those previously observed with another beta-blocker, propranolol, suggest that tubular beta-receptors are not involved in the synthesis of PGs. The different hemodynamic effects of the two drugs are the most likely explanation for the different responses in prostaglandin excretion.