ENDOMETRIOMA OF THE LIVER

Hepatic endometriosis is extremely rare. The diagnosis is often missed and treatment is delayed. A 37-year-old woman was referred to the gynaecology department with vague abdominal pains. She had a past history of pelvic endometriosis and hysterectomy with bilateral salpingo-oophorectomy. Further investigations in due course confirmed it to be endometriosis of the liver. She was eventually referred to the hepatobiliary unit, almost three years after her first presentation, where she was operated on with good results.     

Successful Treatment of Bone Marrow Failure in Gaucher's Disease with Low-dose Modified Glucocerebrosidase

We report the beneficial effects of enzyme replacement therapywith mannose-terminated human glucocerebrosidase (‘Ceredase’)in a patient suffering from transfusion-dependent bone marrowfailure due to Gaucher's disease. Treatment with low-dose enzymeinfusions, given twice weekly, rapidly reversed the haematopoieticfailure and incapacitating skeletal disease. It appears likelythat prior splenectomy favourably influenced the response tothis therapy.     

Increased number of substitutions in the D-loop of mitochondrial DNA in the sudden infant death syndrome

The purpose of the present study was to investigate substitutions in the D-loop of mitochondrial DNA (mtDNA) in sudden infant death syndrome (SIDS) and controls, since several observations indicate the involvement of mtDNA mutations in SIDS. These include elevated levels of vitreous humour hypoxanthine in SIDS victims, familial clustering without mendelian traits, and observations of increased sleepiness and a lower activity score in infants who later succumbed to SIDS. Eighty-two cases of SIDS and 133 controls were investigated and the D-loop sequences were recorded in the base-pair range 16 055-16 500 in the mtDNA sequence. The sequencing was carried out using the Applied Biosystems Sequenase dye terminator method and a ABD373A sequencer. The recorded D-loop sequences were compared with the Cambridge sequence and differences were recorded as substitutions. The SIDS cases had a tendency towards a higher substitution rate in the D-loop than the controls ( p = 0.088). This observation makes it interesting to search for deleterious mutations in other locations in the mtDNA.     

Novel piperidine sigma receptor ligands as potential antipsychotic drugs.

sigma receptor ligands represent a new class of potential antipsychotic drugs. This paper presents the structure-activity relationships leading to novel disubstituted piperidine sigma ligands, which have little or no affinity for dopamine D2 receptors. Selectivity for sigma sites over dopamine D2 or serotonin 5-HT2 receptors appears to be governed by the chemical nature of the piperidine nitrogen substituent, its distance from the basic nitrogen, and its orientation relative to the other piperidine substituent. Several of these compounds have good oral potency in some animal models used to evaluate potential antipsychotic drugs. The N-cyclopropylmethyl ketones and ethers (e.g. 6i (DuP 734), 6q, 18a, and 18n) have the best in vivo potency. Compounds 6i (DuP 734) and 6q did not cause catalepsy in the rat, even at very high doses. On the basis of the pharmacology profiles of these sigma ligands, we propose these compounds may be effective antipsychotic drugs, which do not induce extrapyramidal side effects or tardive dyskinesia.     

Psychiatric and metabolic characteristics of childhood versus adult-onset obesity in patients seeking weight management

The purpose of the study was to examine whether childhood-onset obesity differed from adult-onset obesity in lifetime prevalence of mood and eating disorders, and metabolic abnormalities, in currently obese adults seeking weight loss. A subgroup of childhood-onset obesity participants (N=44) was compared with a subgroup with adult-onset obesity (N=69) on a number of clinical and metabolic features. The results showed high lifetime prevalence rates of mood (78%) and eating (81%) disorders, and metabolic syndrome (45%), in the group as a whole. However, patients with childhood-onset obesity had a significantly higher lifetime prevalence of eating disorders in general, and of bulimia nervosa in particular, than patients with adult-onset obesity. Our results support findings of substantial comorbidity among obesity, mood and eating disorders, and metabolic syndrome in weight loss seeking populations. Early recognition and attention to eating and mood dysregulation, including, but not limited to binge eating disorder and bulimia nervosa, in some persons, might help reduce their lifetime risk for obesity.     

Fenfluramine, p-chloroamphetamine and p-fluoroamphetamine stimulation of pituitary-adrenocortical activity in rat: evidence for differences in site and mechanism of action

Serum corticosterone concentrations were measured in rats after injection of fenfluramine (FEN), p-chloroamphetamine (PCA) and p-fluoroamphetamine (PFA), halogenated amphetamine derivatives believed to exert their behavioral and physiological effects through the release and/or depletion of brain serotonin (5-HT). Animals were pretreated with various serotonergic drugs before FEN, PCA or PFA in order to ascertain the role of 5-HT in mediating the pituitary-adrenocortical response to each compound. Systemic administration of FEN, PCA or PFA caused a dose-dependent corticosterone elevation, with a potency rank ordering of PCA greater than FEN greater than PFA. Chronic depletion of brain 5-HT by pretreatment with p-chlorophenylalanine or 5,7-dihydroxytryptamine antagonized the PCA-induced elevation, but not that produced by FEN or PFA. When injected i.c.v., PCA and PFA elevated corticosterone levels whereas FEN did not. The central PCA-induced elevation was prevented by pretreatment with either the 5-HT reuptake inhibitor fluoxetine or the 5-HT receptor blocker methysergide. Fluoxetine or methysergide also antagonized the corticosterone elevation produced by systemically injected PCA or FEN, but not that produced by PFA. In the final experiment, pretreatment with dexamethasone, an inhibitor of pituitary adrenocorticotropic hormone secretion, prevented the corticosterone elevation produced by all three drugs. Thus, despite their structural and pharmacological similarities, FEN, PCA and PFA each act differently to stimulate corticosterone secretion. As expected, PCA elevates corticosterone levels through a central serotonergic mechanism that requires the continued synthesis and storage of 5-HT.(ABSTRACT TRUNCATED AT 250 WORDS)     

EMR documentation of physician–patient communication following genomic counseling for actionable complex disease and pharmacogenomic results

Genomic risk information for potentially actionable complex diseases and pharmacogenomics communicated through genomic counseling (GC) may motivate physicians and patients to take preventive actions. The Ohio State University‐Coriell Personalized Medicine Collaborative is a randomized trial to measure the effects of in‐person GC on chronic disease patients provided with multiplex results. Nine personalized genomic risk reports were provided to patients through a web portal, and to physicians via electronic medical record (EMR). Active arm participants (98, 39% female) received GC within 1 month of report viewing; control arm subjects (101, 54% female) could access counseling 3‐months post‐report viewing. We examined whether GC affected documentation of physician–patient communication by reviewing the first clinical note following the patient's GC visit or report upload to the EMR. Multivariable logistic regression modeling estimated the independent effect of GC on physician–patient communication, as intention to treat (ITT) and per protocol (PP), adjusted for physician educational intervention. Counselees in the active arm had more physician–patient communications than control subjects [ITT, odds ratio (OR): 3.76 (95% confidence interval (CI): 1.38–10.22, p < 0.0094); PP, OR: 5.53 (95% CI: 2.20–13.90, p = 0.0017). In conclusion, GC appreciably affected physician–patient communication following receipt of potentially actionable genomic risk information.