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PubMed2000

Fasting exacerbates acute pancreatitis by occlusion of the common bile duct in rats.

We examined the effects of fasting and non-fasting on gallstone-related acute pancreatitis by the occlusion of the common bile duct (OCD). We prepared a rat OCD-induced pancreatitis model under both fasting and non-fasting conditions, and we measured amylase activity in ascites as well as production of inflammatory cytokines and chemokines. We also examined the pathology of the pancreas, myeloperoxidase (MPO) activity in some tissues and mortality rates. In the fasted OCD group, ascites containing a large amount of amylase, interleukin 1beta (IL-1beta), interleukin 6 (IL-6), and cytokine-induced neutrophil chemoattractant-1 (CINC-1) as well as marked hemorrhage and necrosis of the pancreatic acinar cells were observed. Pulmonary MPO activity increased 3.4-fold compared to the control group. In the non-fasted OCD group, there was no development of ascites. Slight necrosis of acinar cells and slight increases in pulmonary MPO activity were observed. In addition, in the fasted OCD group, the cumulative mortality rate was 50% 6 days after ligation. However, in the non-fasted OCD group, none of the animals died. These results suggest that gallstone-related severe pancreatitis depends on fasting-related structural and/or functional changes in the pancreas. Moreover, increased production of inflammatory cytokines and chemokines in ascites under fasting condition may be involved in multiple organ failure resulting from severe acute pancreatitis.

Acute Disease↗
PubMed2004

Personality characteristics in obsessive-compulsive disorder and individuals with subclinical obsessive-compulsive problems.

OBJECTIVE: To assess the relationship between normal personality traits and obsessive-compulsive (OC) phenomena in individuals with subclinical OC problems and patients whose problems met diagnostic criteria for obsessive-compulsive disorder (OCD). METHOD: In Study 1, 25 healthy volunteers with high scores on the Padua Inventory (PI) and 28 controls with low scores on the PI were compared on the Sensitivity to Punishment and Sensitivity to Reward Questionnaire (SPSRQ), the Eysenck Personality Questionnaire (EPQ), and measures of depression and state anxiety. In Study 2, 56 treatment-seeking participants meeting DSM-IV criteria for OCD and 40 healthy volunteers of similar sociodemographic characteristics were compared on the same measures. RESULTS: Both individuals with subclinical OC problems and OCD patients scored significantly higher than their respective control groups on sensitivity to punishment, neuroticism and psychoticism. OCD patients, but not individuals with subclinical OC problems, scored lower in extraversion than their respective controls. Neuroticism was the strongest predictor of high scores on the PI in Study 1, while psychoticism was the strongest predictor of the presence of an OCD diagnosis in Study 2. CONCLUSION: Healthy participants with high scores on OC measures and OCD patients share various personality traits but can also be distinguished according to the level of extraversion, neuroticism and psychoticism.

Adolescent↗
PubMed1997

Animal models with potential applications for screening compounds for the treatment of obsessive-compulsive disorder.

The availability of an animal model for obsessive-compulsive disorder (OCD) is necessary for the development of novel pharmacological treatments. To be useful, the model must be predictive of clinical performance, possess characteristic criteria and distinguish anti-OCD from antidepressant compounds. Due to the lack of OCD models useful for drug discovery, all compounds currently used for OCD were developed first as antidepressants. In this article, we discuss the relative merits of: stereotypic behaviours (canine acral lick, feather picking, amphetamine- and 5-HT-induced stereotypy); adjunctive and displacement behaviours (schedule-induced polydipsia, wheel running, resident-intruder grooming); anxiolytic tests (separation and shock-induced ultrasonic vocalisation and marble burying); and depression tests (inescapable shock-induced escape and immobility in forced swim) as potential OCD models. We conclude that adjunctive and displacement behaviours, and in particular schedule-induced polydipsia, may prove to be the best models for compulsive behaviour in animals that can be used for the discovery of novel anti-OCD agents.

Journal Article↗
PubMed2002

Spotlight on fluvoxamine in anxiety disorders in children and adolescents.

Fluvoxamine is a selective serotonin reuptake inhibitor (SSRI) which may be used for the management of anxiety disorders in children and adolescents. Absorption of fluvoxamine was similar in adolescents to that in adults, which suggests that the maximum dosage of the drug for patients aged between 12 and 17 years can be as high as 300 mg/day. However, steady-state plasma fluvoxamine concentrations were 2 to 3 times higher in children (aged between 6 and 11 years) than in adolescents; thus, the maximum fluvoxamine dosage recommended for children is 200 mg/day. Fluvoxamine (50 to 300 mg/day) for 8 to 16 weeks significantly reduced symptoms of obsessive-compulsive disorder (OCD) [measured across multiple assessment scales] compared with placebo in a well controlled trial in paediatric patients (n = 120) or from baseline in noncomparative trials in adolescent (n = 20) or paediatric (n = 16) patients. Improvements with fluvoxamine (up to 200 mg/day) were observed for up to 1 year in 98 patients with OCD in a noncomparative trial. The drug (up to 250 or 300 mg/day) also improved symptoms of anxiety compared with placebo in an 8-week well controlled trial in 128 paediatric patients with social phobia, separation anxiety disorder or generalised anxiety disorder (GAD). Fluvoxamine (50 to 300 mg/day) appears to be well tolerated in paediatric patients, with most adverse events with the drug (except abdominal discomfort, which occurred more often in patients receiving fluvoxamine) occurring with a similar incidence to those with placebo. The most common adverse events involved the CNS or gastrointestinal system. Most adverse events reported by paediatric patients with OCD were similar to those reported by adults. In conclusion, fluvoxamine is generally well tolerated and has demonstrated short-term efficacy compared with placebo in the treatment of OCD, and social phobia, separation anxiety disorder or GAD in well controlled trials in paediatric patients. Reductions in symptoms of anxiety with fluvoxamine have been observed for up to 1 year in children and adolescents with OCD. However, there are currently no comparative trials of fluvoxamine with other pharmacological agents. In the absence of such trials, current consensus opinion recommends that when pharmacotherapy is indicated, fluvoxamine, like other SSRIs, can be used as first-line treatment for anxiety disorders, particularly OCD, in paediatric patients. However, direct comparisons are required to assess the relative efficacy and tolerability of pharmacological agents in order to make firm recommendations for the treatment of anxiety disorders in this patient group.

Adolescent↗
PubMed2001

Occupational contact dermatitis. Recognition and management.

Occupational contact dermatitis (OCD) represents 90 to 95% of all occupational dermatoses. The incidence rate of OCD is estimated to be around 0.5 to 1.9 cases per full-time worker per year. However, epidemiologic data are lacking and incidence is probably underestimated, especially in the US. Over the past 20 years, OCD has been the most frequently reported occupational disorder to German social insurance institutions. Critical factors in the management of OCD are recognition of clinical features, knowledge of allergens and irritants present in different occupational fields, knowledge of suitable protection, interpretation of patch test results, and awareness of medicolegal aspects. Management of OCD should be carried out by dermatologists and patch test clinics in cooperation with physicians specialized in industrial medicine. Individuals at high risk of OCD are hairdressers, dental laboratory technicians, other healthcare workers, construction industry workers, metal workers, leather and shoe manufacturers, florists and gardeners, and bakers, caterers, confectioners and cooks.

Dermatitis, Occupational↗
PubMed2001

Fluvoxamine: a review of its therapeutic potential in the management of anxiety disorders in children and adolescents.

Fluvoxamine is a selective serotonin reuptake inhibitor (SSRI) which may be used for the management of anxiety disorders in children and adolescents. Absorption of fluvoxamine was similar in adolescents to that in adults, which suggests that the maximum dosage of the drug for patients aged between 12 and 17 years can be as high as 300 mg/day. However, steady-state plasma fluvoxamine [corrected] concentrations were 2 to 3 times higher in children (aged between 6 and 11 years) than in adolescents; thus, the maximum fluvoxamine dosage recommended for children is 200 mg/day. Fluvoxamine (50 to 300 mg/day) for 8 to 16 weeks significantly reduced symptoms of obsessive-compulsive disorder (OCD) [measured across multiple assessment scales] compared with placebo in a well controlled trial in paediatric patients (n = 120) or from baseline in noncomparative trials in adolescent (n = 20) or paediatric (n = 16) patients. Improvements with fluvoxamine (up to 200 mg/day) were observed for up to 1 year in 98 patients with OCD in a noncomparative trial. The drug (up to 250 or 300 mg/day) also improved symptoms of anxiety compared with placebo in an 8-week well controlled trial in 128 paediatric patients with social phobia, separation anxiety disorder or generalised anxiety disorder (GAD). Fluvoxamine (50 to 300 mg/day) appears to be well tolerated in paediatric patients, with most adverse events with the drug (except abdominal discomfort, which occurred more often in patients receiving fluvoxamine) occurring with a similar incidence to those with placebo. The most common adverse events involved the central nervous system or gastrointestinal system. Most adverse events reported by paediatric patients with OCD were similar to those reported by adults. In conclusion, fluvoxamine is generally well tolerated and has demonstrated short-term efficacy compared with placebo in the treatment of OCD, and social phobia, separation anxiety disorder or GAD in well controlled trials in paediatric patients. Reductions in symptoms of anxiety with fluvoxamine have been observed for up to 1 year in children and adolescents with OCD. However, there are currently no comparative trials of fluvoxamine with other pharmacological agents. In the absence of such trials, current consensus opinion recommends that when pharmacotherapy is indicated, fluvoxamine, like other SSRIs, can be used as first-line treatment for anxiety disorders, particularly OCD, in paediatric patients. However, direct comparisons are required to assess the relative efficacy and tolerability of pharmacological agents in order to make firm recommendations for the treatment of anxiety disorders in this patient group.

Adolescent↗
PubMed2000

Serum cholesterol in patients with obsessive compulsive disorder during treatment with behavior therapy and SSRI or placebo.

OBJECTIVE: Patients with panic disorder are reported to have elevated cholesterol levels. There is also some evidence that cholesterol elevation is not so much a specific condition in panic disorder but is generally associated with anxiety. So far, there is little data on cholesterol levels in patients with obsessive compulsive disorders (OCD) which is also classified as anxiety disorder. METHOD: Thirty-three patients with OCD participated in the study. Serum cholesterol was measured as pretreatment and at the end of a ten-week treatment-period. All patients received behavior therapy and, in a double-blind fashion, fluvoxamine or placebo. Severity of OCD was assessed by the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). RESULTS: Pretreatment cholesterol values of OCD patients were compared with cholesterol levels of thirty panic disorder patients and thirty normal controls. OCD patients had elevated cholesterol levels comparable with those of panic disorder patients. Cholesterol levels decreased significantly from pre- to posttreatment. OCD patients with high cholesterol levels (> or = 240 mg/dl, n = 7) could make best use of the treatment whereas patients with desirable cholesterol levels (< 200 mg/dl, n = 11) did not change their cholesterol during treatment. CONCLUSIONS: Our data support the assumption that not only panic disorder but also other anxiety disorders, e.g., obsessive compulsive disorders, may be associated with serum cholesterol elevations. Effective treatment (behavior therapy and/or treatment with a selective serotonin reuptake inhibitor [SSRI]) seems to decrease cholesterol levels, especially in patients with pathological cholesterol elevations.

Adult↗
PubMed2001

Obsessive-compulsive disorder and immunocompetence.

OBJECTIVE: A postinfectious, autoimmune response may be associated with the development of pediatric obsessive-compulsive disorder (OCD). According to this model, antistreptococcal antibodies cross-react with basal ganglia neurons following streptococcus infection. This autoimmune reaction disrupts a basal ganglia-thalamocortical circuit and generates obsessive-compulsive symptoms. One implication of this model is that prolonged immunologic stress may be a risk factor for OCD. That is, immunologic stress may compromise the blood-brain barrier and permit the influx of antistriatal antibodies into the central nervous system. This article explores one part of this putative relationship by investigating whether adult OCD patients, compared to members of other psychiatric groups, demonstrate a higher incidence of recurrent infections and other conditions suggestive of compromised immune function. METHOD: To test this hypothesis, we conducted a medical records review of 100 consecutive patients evaluated at a private psychiatric clinic specializing in the treatment of anxiety disorders. Sixty-five patients met diagnostic criteria for an Axis-I syndrome. Primary diagnoses included OCD, posttraumatic stress disorder, social anxiety disorder, generalized anxiety disorder, panic disorder with agoraphobia, and dysthymic disorder. Each medical record was reviewed for the presence of target syndromes or presenting symptoms suggestive of compromised immune function. RESULTS: Chart review revealed an increased rate of immune-related symptoms and syndromes among OCD patients in comparison to other anxiety and mood disorder groups. Groups did not differ significantly in the incidence of non-immune symptoms and syndromes. CONCLUSION: Adult OCD patients appear to have an increased rate of immune-related diseases above and beyond that seen in other psychiatric disorders.

Adult↗
PubMed1990

Obsessive-compulsive disorder: an exploration of some unresolved clinical issues.

The study data were obtained from a questionnaire survey of a South Australian community support group for obsessive-compulsive disorder (OCD). The response rate was 47%, yielding 81 questionnaire sets completed by members who, on the basis of their questionnaire responses, were judged to meet DSM-III-R criteria for OCD. The clinical and demographic characteristics of the respondents were very similar to those of previously reported clinical populations. Mean age at onset of OCD was 18 years and mean duration 17 years; 55% of respondents rated their current OCD as extremely or very severe. Seventy-seven percent had received psychiatric treatment (mean 55 occasions) and 47% had attended clinical psychologists or professional counsellors (mean 20 occasions). Those who reported prominent fears of losing control of motor behaviours had received a significant excess of outpatient and inpatient psychiatric treatment. Most respondents reported the presence of all 4 identified components of OCD, of which the obsession/rumination component was central. Levels of OCD correlated strongly with levels of overall psychopathology, and fertility rates were significantly reduced in those patients who reported the most symptoms.

Adult↗
PubMed2003

Treatment of patients with intractable obsessive-compulsive disorder with anterior capsular stimulation. Case report.

Obsessive-compulsive disorder (OCD) is a common, chronic, disabling anxiety disorder characterized by recurrent obsessive thoughts and uncontrolled repetitive acts. Although many patients respond to various pharmacological treatments, there is a cohort of patients with intractable or refractory disease. The authors present the case of a patient with intractable OCD who was treated with bilateral electrical stimulators, which were stereotactically placed in the anterior limbs of the internal capsules. Following psychiatric consultation and 10 years of empirical medication regimens for OCD, a woman was referred for neurosurgical evaluation. After informed consent had been obtained from the patient, the authors placed bilateral stimulator leads in the anterior limbs of the internal capsules. The stereotactic coordinates were based on data in pertinent current literature. The stimulation parameters, which are presented in this paper, were set at 2 weeks and reviewed at 6 weeks and 3 months postoperatively. No changes were required. Postoperative analysis included evaluation by the patient's referring psychiatrist, a second independent psychiatrist, and pre- and postoperative administration of the Yale-Brown Obsessive Compulsive Scale. A marked improvement was noted in thispatient's OCD symptomatology and general psychosocial function. Previous documentation of patient responses to psychosurgical procedures for intractable or refractory OCD has been met with little enthusiasm, presumably because of the invasiveness and irreversibility of the surgery. In this report the authors suggest that deep brain stimulation of appropriate targets may be an effective and safe treatment for certain patients with OCD and a potentially reversible treatment for those patients who do not obtain therapeutic benefit.

Adult↗
PubMed2004

Effect of subthalamic nucleus stimulation on obsessive-compulsive disorder in a patient with Parkinson disease. Case report.

The authors report on a patient with Parkinson disease (PD) and severe obsessive-compulsive disorder (OCD), in whom bilateral stimulation of the subthalamic nucleus (STN) was used to treat both PD and OCD symptoms. This 49-year-old man had displayed symptoms of PD for 13 years. Progressively, his motor disability became severe despite optimal medical treatment. In parallel, he suffered severe OCD for 16 years, with obsessions of accumulation and compulsions of gathering and rubbing that lasted more than 8 hours per day. Bilateral high-frequency STN stimulation was performed to treat motor disability. After surgery (at 1-year follow up), motor and OCD symptoms were dramatically improved. The pre- and postoperative Yale-Brown Obsessive-Compulsive Scale scores were 32 and 1, respectively. No additional antiparkinsonian drugs were administered. This case and other recent reports indicate that OCD symptoms can be improved by deep brain stimulation, a finding that opens new perspectives in the surgical treatment of severe and medically intractable OCD.

Electric Stimulation Therapy↗
PubMed2006

A functional neuroimaging investigation of deep brain stimulation in patients with obsessive-compulsive disorder.

OBJECT: Deep brain stimulation (DBS) of the ventral [anterior internal] capsule/ventral striatum (VC/VS) is under investigation as an alternative to anterior capsulotomy for severe obsessive-compulsive disorder (OCD). In neuroimaging studies of patients with OCD, dysfunction in the orbitofrontal and anterior cingulate cortex, striatum, and thalamus has been identified; and modulation of activity in this circuit has been observed following successful nonsurgical treatment. The purpose of the current study was to test hypotheses regarding changes in regional cerebral blood flow (rCBF) during acute DBS at the VC/VS target in patients with OCD who were participating in a clinical DBS trial. METHODS: Six patients enrolled in a DBS trial for OCD underwent positron emission tomography to measure rCBF; the rCBF measured during acute DBS at high frequency was then compared with those measured during DBS at low frequency and off (control) conditions. On the basis of neuroanatomical knowledge about the VC/VS and neuroimaging data on OCD, the authors predicted that acute DBS at this target would result in modulation of activity within the implicated frontal-basal ganglia-thalamic circuit. Data were analyzed using statistical parametric mapping. In a comparison of acute high-frequency DBS with control conditions, the authors found significant activation of the orbitofrontal cortex, anterior cingulate cortex, striatum, globus pallidus, and thalamus. CONCLUSIONS: Acute DBS at the VC/VS target is associated with activation of the circuitry implicated in OCD. Further studies will be necessary to replicate these findings and to determine the neural effects associated with chronic VC/VS DBS. Moreover, additional data are needed to investigate whether pretreatment imaging profiles can be used to predict a patient's subsequent clinical response to chronic DBS.

Adult↗
PubMed1999

Patterns of remission and relapse in obsessive-compulsive disorder: a 2-year prospective study.

OBJECTIVE: This study examined the course of illness in patients with obsessive-compulsive disorder (OCD) over a 2-year period. METHOD: Sixty-six patients with a primary diagnosis of DSM-III-R OCD were followed prospectively for 2 years. Baseline information was collected on demographic characteristics, Axis I and II diagnoses, and severity of OCD symptoms. Follow-up measures obtained at 3, 6, 12, and 24 months after baseline assessment included information on symptomatic and diagnostic status as well as behavioral and somatic treatments received. RESULTS: The probability of full remission from OCD over the 2-year period was 12%. The probability of partial remission was 47%. After achieving remission from OCD, the probability of relapse was 48%. No factors were identified that significantly predicted full or partial remission. Seventy-seven percent (N = 51) of the subjects received a serotonin reuptake inhibitor (SRI) for > or =12 weeks, and 68% (N = 45) received medium-to-high doses of SRIs for > or =12 weeks. Only 18% received a full trial of behavior therapy. CONCLUSION: Despite exposure to at least 1 adequate trial of an SRI, the likelihood of full remission of OCD in this study was low. Results of this study also suggest that behavior therapy may be under-utilized.

Adult↗
PubMed1999

Cognitive-behavioral therapy as an adjunct to serotonin reuptake inhibitors in obsessive-compulsive disorder: an open trial.

BACKGROUND: We report the results of an open trial of cognitive-behavioral therapy (CBT) using exposure and ritual prevention as an adjunct to serotonin reuptake inhibitors (SRIs) in obsessive-compulsive disorder (OCD). We hypothesized that exposure and ritual prevention would significantly reduce OCD symptoms in patients who remained symptomatic despite an adequate trial of an SRI and enable patients to discontinue their medication. METHOD: OCD patients taking an adequate dose of an SRI > or = 12 weeks who remained symptomatic (i.e., a Yale-Brown Obsessive Compulsive Scale [Y-BOCS] score > or = 16) were eligible. While taking a stable dose of an SRI, patients received 17 sessions of exposure and ritual prevention. For the intent-to-treat group, the paired t test was used to compare scores on the Y-BOCS, the National Institute of Mental Health (NIMH) Global OCD scale, the Clinical Global Impressions scale, and the Hamilton Rating Scale for Depression before and after exposure and ritual prevention. RESULTS: Six of 7 eligible patients entered the study, and 5 completed it. All 6 improved on all OCD measures. The mean +/- SD Y-BOCS score was 23.8 +/- 2.6 prior to exposure and ritual prevention and 12.2 +/- 4.3 after it (p < .001). The mean percentage decrease on the Y-BOCS was 49% (range, 26%-61%). Patients were rated by the therapist and rated themselves as much (N = 4) or very much (N = 2) improved. Blood drug levels did not change in most patients during exposure and ritual prevention; thus, the improvement was attributed to this type of therapy. No patients discontinued their medication. CONCLUSION: This open trial suggests that CBT using exposure and ritual prevention can lead to a significant reduction in OCD symptoms in patients who remain symptomatic despite an adequate trial of an SRI.

Ambulatory Care↗
PubMed2000

Olanzapine augmentation for treatment-resistant obsessive-compulsive disorder.

BACKGROUND: Adding the atypical neuroleptic risperidone to a serotonin reuptake inhibitor (SRI) has benefited patients with treatment-refractory obsessive-compulsive disorder (OCD). Since olanzapine and risperidone have similar serotonergic and dopaminergic receptor binding profiles, we tested the hypothesis that olanzapine augmentation would be beneficial in treatment-unresponsive OCD. METHOD: For this 8-week trial, we recruited 10 adult OCD patients (DSM-IV criteria) unresponsive to fluoxetine (> or =60 mg/day) for > or =10 weeks, which was continued throughout the trial. Other psychotropic medications were discontinued. Subjects had OCD for > or =1 year, a Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score of > or =18, and no organic, psychotic, or other primary Axis I disorder. Two weeks after olanzapine, 2.5 mg/day, was added, and in the absence of responder status (Y-BOCS score decrease > or =25%) and limiting side effects, we increased the dose to 5 mg/day, and after 2 more weeks, to 10 mg/day for 4 weeks. RESULTS: The subjects had failed a mean of 3.3 SRI trials (range, 1-5) and had a mean +/- SD baseline Y-BOCS score of 29.0 +/- 4.9. Nine patients completed the trial. The subjects' mean +/- SD endpoint Y-BOCS score was 24.4 +/- 8.0 (a 16% decrease). The 3 responders' Y-BOCS scores dropped 68%, 30%, and 29%, but only 1 patient was rated "much improved." He maintained this improvement during a 6-month follow-up period taking olanzapine, 5 mg/day. Improvement in OCD was independent of improvement in mood symptoms. Six patients (60%) experienced significant weight gain. CONCLUSION: Olanzapine augmentation may benefit treatment-unresponsive OCD. Double-blind, placebo-controlled trials are warranted along with trials comparing risperidone and olanzapine augmentation.

Adult↗
PubMed2005

Bupropion for patients with obsessive-compulsive disorder: an open-label, fixed-dose study.

OBJECTIVE: In the present study, we examined the efficacy of bupropion for patients with obsessive-compulsive disorder (OCD). METHOD: Twelve patients with OCD according to DSM-IV criteria were included in an open trial with bupropion, maximum dosage 300 mg per day, during 8 weeks. The primary efficacy parameter was the Yale-Brown Obsessive Compulsive Scale (YBOCS). A responder was defined by a reduction in score on the YBOCS of > or = 25%. Data were collected from February 2003 to July 2003. RESULTS: An intent-to-treat analysis using the last observation carried forward demonstrated that bupropion had no mean effect on OCD symptoms (mean YBOCS decrease was 1.1 +/- 9.6). Four patients improved, with a mean decrease on the YBOCS of 31%, and 2 of them met responder rate criteria. Eight patients experienced an exacerbation of OCD symptoms, with a mean increase on the YBOCS of 21%. CONCLUSION: Bupropion is not an effective treatment for OCD, but the bimodal distribution of the effect supports the notion that dopamine might be involved in the pathophysiology of OCD.

Adult↗
PubMed2006

Safety, tolerability, and efficacy of psilocybin in 9 patients with obsessive-compulsive disorder.

BACKGROUND: Anecdotal reports suggest that psychedelic agents may relieve symptoms of obsessive-compulsive disorder (OCD). This modified double-blind study investigated the safety, tolerability, and clinical effects of psilocybin, a potent 5-HT(1A) and 5-HT(2A/2C) agonist, in patients with OCD. METHOD: Nine subjects with DSM-IV-defined OCD and no other current major psychiatric disorder participated in up to 4 single-dose exposures to psilocybin in doses ranging from sub-hallucinogenic to frankly hallucinogenic. Low (100 microg/kg), medium (200 microg/kg), and high (300 microg/kg) doses were assigned in that order, and a very low dose (25 microg/kg) was inserted randomly and in double-blind fashion at any time after the first dose. Testing days were separated by at least 1 week. Each session was conducted over an 8-hour period in a controlled environment in an outpatient clinic; subjects were then transferred to a psychiatric inpatient unit for overnight observation. The Yale-Brown Obsessive Compulsive Scale (YBOCS) and a visual analog scale measuring overall obsessive-compulsive symptom severity were administered at 0, 4, 8, and 24 hours post-ingestion. The Hallucinogen Rating Scale was administered at 8 hours, and vital signs were recorded at 0, 1, 4, 8, and 24 hours after ingestion. The study was conducted from November 2001 to November 2004. RESULTS: Nine subjects were administered a total of 29 psilocybin doses. One subject experienced transient hypertension without relation to anxiety or somatic symptoms, but no other significant adverse effects were observed. Marked decreases in OCD symptoms of variable degrees were observed in all subjects during 1 or more of the testing sessions (23%-100% decrease in YBOCS score). Repeated-measures analysis of variance for all YBOCS values revealed a significant main effect of time on Wilks lambda (F = 9.86, df = 3,3; p = .046), but no significant effect of dose (F = 2.25, df = 3,3; p = .261) or interaction of time and dose (F = 0.923, df = 9,45; p = .515). Improvement generally lasted past the 24-hour timepoint. CONCLUSIONS: In a controlled clinical environment, psilocybin was safely used in subjects with OCD and was associated with acute reductions in core OCD symptoms in several subjects.

Adult↗
PubMed2000

Oxychlordane and trans-nonachlor in breast adipose tissue and risk of female breast cancer.

BACKGROUND: Organochlorine compounds, including organochlorine pesticides, have been suggested by some, but not all, studies to be associated with female breast-cancer risk. So far, studies relating organochlorine compounds and breast-cancer risk have mainly focused on polychlorinated biphenyls (PCBs) and dichlorodiphenyltrichloroethane (DDT) as risk factors for female breast cancer. This paper examines the hypothesis that environmental exposure to trans-nonachlor (TNC) and oxychlordane (OCD), a major metabolite of the insecticide chlordane, increases the METHODS: A total of 304 histologically confirmed, incident primary breast-cancer patients and 186 histologically confirmed incident benign breast-disease controls were included in the study between 1994 and 1997. Breast adipose tissue not needed for diagnostic purposes was collected and analysed for TNC, OCD and other organochlorine compounds. A standardised, structured questionnaire was used to obtain information on major known, or suspected, risk factors for breast cancer. RESULTS: The age and lipid-adjusted geometric mean adipose-tissue levels of OCD were similar between the cases [36.4 p.p.b., 95% confidence interval (CI) 34.7-38.2 p.p.b.] and controls (38.0 p.p.b., 95% Cl 35.7-40.6 p.p.b.). The age and lipid-adjusted geometric mean adipose-tissue levels of TNC between the cases (55.5 p.p.b., 95% CI 52.6-58.5 p.p.b.) and controls (58.1 p.p.b., 95% CI 54.2-62.3 p.p.b.) were also similar. There was no association between breast-cancer risk and mean adipose-tissue levels of OCD and TNC. The covariate-adjusted odds ratio (OR) was 0.7 (95% CI 0.4-1.3) for OCD and 1.1 (95% CI 0.6-1.9) for TNC, when the highest quartile was compared with the lowest. The risk also did not vary based on oestrogen or progesterone receptor status or menopausal status. DISCUSSION: We found no significantly increased risk of breast cancer associated with breast adipose-tissue levels of OCD or TNC; this is consistent with recent epidemiological studies, indicating that environmental exposure to organochlorine compounds does not have an overall significant impact on breast-cancer risk.

Adipose Tissue↗