CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 9 2007
EI Boesen
SUMMARY 1Pathological changes to the kidney, such as vascular remodelling, have been found in several models of hypertension and may contribute to the maintenance of hypertension or confer susceptibility to redeveloping hypertension after the original prohypertensive stimulus is withdrawn. 2To investigate whether noradrenaline-induced hypertension induces persistent, functionally important changes to the kidney, the acute pressure,natriuresis relationship was characterized in anaesthetized rats under controlled neural and hormonal conditions following chronic (14 days) intravenous infusion of noradrenaline (48 µg/kg per h) or vehicle (0.04 mg/mL ascorbic acid and 0.156 mg/mL NaH2PO4·2H2O in 10 IU/mL heparinized saline). 3Conscious mean arterial pressure was significantly elevated by infusion of noradrenaline at 48 µg/kg per h (+10 ± 2 mmHg at Day 14; P < 0.01 vs vehicle group). The acute relationships between arterial pressure and renal blood flow, glomerular filtration rate, Na+ excretion and urine flow were not significantly different between the noradrenaline- and vehicle-infused rats immediately after termination of noradrenaline infusion. 4In summary, chronic intravenous noradrenaline infusion did not cause persistent changes in renal function, indicating that, in contrast with many models of hypertension, this model does not induce underlying prohypertensive changes to the kidney. [source]

Ethics Seminars: Withdrawal of Treatment in the Emergency Department,When and How?

ACADEMIC EMERGENCY MEDICINE, Issue 12 2006
Kelly Bookman MD
Abstract Although increasing discussion has occurred within emergency medicine about indications for withholding cardiac life support and other resuscitative interventions, emergency physicians (EPs) may be less familiar with the ethical, legal, and practical issues surrounding withdrawal of life support that has already been initiated. Both physicians and out-of-hospital personnel must act rapidly in critical situations and must assume that the patient has the desire to be resuscitated, unless clear evidence exists to the contrary. Often, only after initial life-saving actions have stabilized the patient is there time to reflect and determine a patient's desires regarding such interventions. When the EP can clearly discern a patient's previously stated wishes during the emergency department (ED) stay, these wishes should be honored in the ED. Respecting a patient's request to avoid unwanted, invasive treatments near death may involve withdrawing interventions that could not be withheld during the first few minutes of care. In this article, the authors use a case of out-of-hospital stabilization of a patient as a springboard to review the ethical and legal framework for withdrawal of life-sustaining care, as well as the practical issues involved with withdrawal of such care in the ED. [source]

Withdrawal of older anticonvulsants for management of status epilepticus: implications for resource-poor countries

DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 4 2005
J M Wilmshurst
No abstract is available for this article. [source]

Editor's Introduction: The Politics of Troop Withdrawal

DIPLOMATIC HISTORY, Issue 3 2010
Marc J. Selverstone
First page of article [source]

Clinical issues in using buprenorphine in the treatment of opiate dependence

DRUG AND ALCOHOL REVIEW, Issue 3 2000
Dr A. Chadderton MB
Abstract This paper looks at the current role of buprenorphine in the treatment of opiate dependence. It suggests that buprenorphine is a useful alternative to methadone and that in at least some cases it may be the preferred option. Buprenorphineis a partial agonist and a partial antagonist with a ceiling of opiate activity probably approximately equal to 30mg methadone. It achieves this at a dose of 10-12mg, although there is considerable individual variation. Because of its ceiling effect it has a good safety profile compared to full agonists such as methadone although some overdose deaths, particularly in conjunction with benzodiazepine abuse, have been reported in France. Induction of buprenorphine may take slightly longer than for methadone and there is a higher dropout rate compared to methadone in the first 2 weeks. This is probably due to the antagonist action of buprenorphine causing more withdrawal symptoms in comparison to methadone. Also, the ceiling effect for buprenorphine means that some clients do not experience sufficient opiate activity to satisfy them. Buprenorphine has a long half-life and dissociates slowly from opiate receptors. Most clients can be dosed second-daily but some find this unacceptable due to mood swings and/or withdrawal symptomson the second day. For these clients daily dosing is required. Transferring from buprenorphine to methadone is straightforward and well tolerated by clients. Transferring from methadone to buprenorphine, however, is more difficult because of the partial antagonist action of buprenorphine. Clients experience withdrawal symptoms that can take up to 2 weeks to settle. Most clients find these symptoms unacceptable when transferring from doses of over 30mg of methadone. The optimum method for transferring from methadone to buprenorphine is still to be determined. Withdrawal from buprenorphine appears to be relatively easier than from methadone. This is presumably due to buprenorphine's partial agonist effect at mureceptors. It is expected that during 2000 buprenorphine will be approved for use in Australia for the treatment of opiate dependence. It may well becomea first-line choice for opiate replacement in heroin dependence. It is also likely to be useful in assisting detoxification fromboth methadone and heroin. [source]

Pregabalin, tiapride and lorazepam in alcohol withdrawal syndrome: a multi-centre, randomized, single-blind comparison trial

ADDICTION, Issue 2 2010
Giovanni Martinotti
ABSTRACT Introduction The aim of this trial was to compare lorazepam with non-benzodiazepine medications such as pregabalin and tiapride in the treatment of alcohol withdrawal syndrome (AWS). These drugs were chosen for their inhibitorial effects on the hypersecretion of neurotransmitters usually observed in AWS. Craving reduction and improvement of psychiatric symptoms were the secondary end-points. Methods One hundred and ninety subjects affected by current alcohol dependence were considered consecutively: 111 were enrolled and divided into three groups of 37 subjects each. Within a treatment duration of 14 days, medication was given up to the following maximum doses (pregabalin 450 mg/day; tiapride 800 mg/day; lorazepam 10 mg/day). Withdrawal (CIWA-Ar), craving [visual analogue scale (VAS); Obsessive and Compulsive Drinking Scale (OCDS)], psychiatric symptoms [Symptom Check List 90 Revised (SCL-90-R)] and quality of life (QL-index) rating scales were applied. Results On the CIWA-Ar score, all the groups showed a significant reduction between times (P < 0.001) with a higher reduction for the pregabalin group (P < 0.01) on items regarding headache and orientation. Retention in treatment was lower in the tiapride group (P < 0.05), while the number of subjects remaining alcohol free was higher in the pregabalin group (P < 0.05). Significant reduction between baseline and the end of the treatment was found in all the groups at the OCDS and the VAS for craving, at the SCL-90-R and QL-index (P < 0.001). Discussion All the medications in the trial showed evidence of safety and efficacy in the treatment of uncomplicated forms of AWS, with some particular differences. The efficacy of pregabalin was superior to that of tiapride, used largely in research trials and, for some measures, to that of the ,gold standard', lorazepam. Accordingly, pregabalin may be considered as a potentially useful new drug for treatment of AWS, deserving further investigation. [source]

Efficacy of repetitive transcranial magnetic stimulation in alcohol dependence: a sham-controlled study

ADDICTION, Issue 1 2010
Biswa R. Mishra
ABSTRACT Objective To study the anticraving efficacy of high-frequency repetitive transcranial magnetic stimulation (rTMS) of the right dorsolateral pre-frontal cortex (DLPFC) in patients with alcohol dependence. Methods We performed a prospective, single-blind, sham-controlled study involving 45 patients with alcohol dependence syndrome (according to ICD-10 DCR), with Clinical Institute of Withdrawal Assessment in Alcohol Withdrawal (CIWA-Ar) scores ,10. Patients were allocated to active and sham rTMS in a 2 : 1 ratio, such that 30 patients received active and 15 patients sham rTMS to the right DLPFC (10 Hz frequency, 4.9 seconds per train, inter-train interval of 30 seconds, 20 trains per session, total 10 sessions). The Alcohol Craving Questionnaire (ACQ-NOW) was administered to measure the severity of alcohol craving at baseline, after the last rTMS session and after 1 month of the last rTMS session. Results Two-way repeated-measures analysis of variance (ANOVA) showed significant reduction in the post-rTMS ACQ-NOW total score and factor scores in the group allocated active rTMS compared to the sham stimulation. The effect size for treatment with time interaction was moderate (,2 = 0.401). Conclusions Right dorsolateral pre-frontal high-frequency rTMS was found to have significant anticraving effects in alcohol dependence. The results highlight the potential of rTMS which, combined with other anticraving drugs, can act as an effective strategy in reducing craving and subsequent relapse in alcohol dependence. [source]

Lady Mary Wroth's Pamphilia to Amphilanthus: The Politics of Withdrawal

ENGLISH LITERARY RENAISSANCE, Issue 3 2000
ROSALIND SMITH
First page of article [source]

Gamma-hydroxybutyric Acid Tolerance and Withdrawal in a Rat Model

ACADEMIC EMERGENCY MEDICINE, Issue 7 2003
Theodore C. Bania MD
Long-term daily use of gamma-hydroxybutyrate (GHB) and related compounds has recently been associated with a withdrawal syndrome. To the best of the authors' knowledge, there are currently no animal models of GHB withdrawal. Objectives: The authors studied and described the effect of chronic dosing of GHB (3,6 days) on tolerance and withdrawal in a rat model. Methods: Rats were administered GHB every three hours via intraperitoneal catheter. Groups of rats (2 per group) were dosed with GHB for either 3 (24 doses), 4 (32 doses), 5 (40 doses), or 6 (48 doses) days. The GHB dose was 0.25 g/kg for doses 1,8, 0.75 g/kg for doses 9,12, 1 g/kg for doses 13,16, 1.25 g/kg for doses 17,24, 1.5 g/kg for doses 25,32, 1.75 g/kg for doses 33,40, and 2 g/kg for doses 41,48. Following the last dose of GHB, the rats were scored using a 16-point ethanol intoxication,withdrawal scale rating spontaneous behaviors, response to handling, grooming, and neurological signs. Lower scores indicate intoxication, while higher scores indicate withdrawal. Scores were recorded at hours 0, 1, 2, 3, 4, 5, 6, 9, 12, and 24. Results:Tolerance: Rats dosed with GHB for more days were less intoxicated one hour after their last GHB dose despite receiving higher doses. Withdrawal: The scores for all rats dosed with GHB increased at hours 4 (p = 0.028), 5 (p = 0.037), 6 (p = 0.007), and 9 (p = 0.024) after the last dose, indicating withdrawal. The scores demonstrated a linear increase dependent upon the number of days of GHB dosing at hours 3 (p < 0.000), 4 (p = 0.004), 5 (p = 0.002), and 12 (p = 0.039) as well as prior to the last dose at hour 0 (p = 0.000). No rats developed seizures. Conclusions: Tolerance and mild withdrawal in rats can be induced by administering intraperitoneal GHB every three hours for 3,6 days. More prolonged dosing and higher doses of GHB may be necessary to induce severe withdrawal. [source]

Antiepileptic Drug Withdrawal after Successful Surgery for Intractable Temporal Lobe Epilepsy

EPILEPSIA, Issue 2 2005
Young Dae Kim
Summary:,Purpose: To investigate the prognosis related to antiepileptic drug (AED) discontinuation after successful surgery for intractable temporal lobe epilepsy. Methods: The clinical courses after temporal lobectomies (TLs) were retrospectively analyzed in 88 consecutive patients. All the patients had TLs as the only surgical procedure, and they had been followed up for longer than 3 years. AED discontinuation was attempted if the patient had been seizure free without aura for ,1 year during the follow-up period. Results: Sixty-six (75%) patients achieved complete seizure freedom for ,1 year; 28 patients were seizure free immediately after surgery (immediate success); and 38 patients became seizure free after some period of recurrent seizures (delayed success). AED discontinuation was attempted in 60 (91%) of 66 patients with a successful outcome. In 13 (22%) patients, seizure relapse developed during AED reduction (n = 60), and in seven (12%) patients after discontinuation of AEDs (n = 38). The seizure recurrence rate was not different between the immediate- and delayed-success groups. Among 20 patients with seizure relapse related to AED tapering, nine (45%) of them regained seizure freedom after reinstitution of AED treatment, and AEDs were eventually discontinued in six of them. Seizures that recurred after complete AED discontinuation had a better prognosis than did the seizures that recurred during AED reduction (seizure freedom in 86% vs. 23%). At the final assessment, 54 (61%) patients had been seizure free ,1 year; 37 without AEDs and 17 with AEDs. The successful discontinuation of AEDs was more frequent for patients with a younger age at the time of surgery and for those patients with shorter disease duration. Conclusions: Our results suggest that seizure freedom without aura at ,1 year is a reasonable indication for the attempt at AED discontinuation. The subsequent control of recurrent seizures was excellent, especially if seizures relapsed after the complete discontinuation of AEDs. Younger age at the time of surgery and a shorter disease duration seem to affect successful AED discontinuation for a long-term period. [source]

Thyroid Function in Girls with Epilepsy with Carbamazepine, Oxcarbazepine, or Valproate Monotherapy and after Withdrawal of Medication

EPILEPSIA, Issue 3 2004
Leena K. Vainionpää
Summary: Purpose: Antiepileptic drugs may affect the serum thyroid hormone concentrations. The aim of this study was to evaluate thyroid function in 78 girls taking carbamazepine (CBZ), oxcarbazepine (OXC), or valproate (VPA) monotherapy for epilepsy and after withdrawal of the treatment. Methods: Forty-one girls taking VPA, 19 taking CBZ, and 18 taking OXC for epilepsy, as well as 54 healthy age-matched controls, aged 8 to 18 years, participated in the study. All the girls were examined clinically, and their pubertal stage was assessed. Blood samples were obtained for thyroid hormone and antibody assays. These examinations were repeated after a mean follow-up of 5.8 years to assess thyroid function, and 64 (82%) of 78 patients and 42 (78%) of 54 controls agreed to participate in the second evaluation. Results: In the first evaluation, the mean serum thyroid hormone concentrations were lower in the girls taking CBZ [thyroxine (T4), 70.2; SD, 10.9 nM; and free thyroxine (FT4), 11.5; SD, 1.8 pM] or OXC (T4, 74.9; SD, 16.4 nM; and FT4, 11.3; SD, 1.8 pM) than in the control girls (T4, 96.6; SD, 15.1 nM, and FT4, 14.4; SD, 1.5 pM; p < 0.001, all comparisons). However, thyrotropin (TSH) concentrations were normal in the girls taking CBZ or OXC. Sixty-three% of the girls taking CBZ and 67% of the girls taking OXC had serum T4 and/or FT4 levels below the lower limit of the reference range. The VPA-treated girls with epilepsy had normal serum T4 and FT4 concentrations, but slightly increased TSH levels (3.3; SD, 1.5 mU/L; p < 0.01) compared with the control girls (2.5; SD, 1.0 mU/L). Normal serum hormone concentrations were restored in the patients who discontinued the medication. Conclusions: Both CBZ and OXC reduce serum thyroid hormone concentrations in girls with epilepsy. Conversely, VPA is associated with normal serum thyroid hormone and increased thyrotropin levels. However, our results suggest that the changes in serum thyroid hormone and thyrotropin levels are reversible after withdrawal of the medication. [source]

Caspase-dependent and -independent apoptosis of mast cells induced by withdrawal of IL-3 is prevented by Toll-like receptor,4-mediated lipopolysaccharide stimulation

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 8 2003
Hideshi Yoshikawa
Abstract IL-3-dependent mucosal-like mast cells undergo apoptosis upon withdrawal of IL-3. Generally, the apoptosis is mediated by the activation of caspases and inhibited by addition of the pan-caspase inhibitors z-VAD-FMK or BOC-D-FMK. However, DNA fragmentation, a typical characteristic of apoptosis, is not inhibited by z-VAD-FMK or BOC-D-FMK in mast cell apoptosis. In this study, we demonstrate that the apoptosis of mast cells is mediated by both caspase-dependent and -independent mechanisms. The caspase-independent apoptosis is mediated by the translocation of endonuclease,G from mitochondria into nuclei. Withdrawal of IL-3 caused down-regulation of Bcl-xL, resulting in a drop in mitochondrial membrane transition potential followed by the release of cytochrome,c and endonuclease,G from mitochondria. However, stimulation of mast cells through Toll-like receptor,4 (TLR4) by lipopolysaccharide prevented mast cell apoptosis by inducing expression of Bcl-xL. Moreover, the activation of mast cells by LPS is enhanced in the presence of IFN-,, which up-regulates the expression of cell surface TLR4. Taken together, these observations provide evidence that mast cells play importantroles not only in allergic reactions but also in innate immunity recognizing enterobacteria through TLR4, and are regulated differently from allergic inflammation by Th1 cytokines. [source]

PRECLINICAL STUDY: Is withdrawal hyperalgesia in morphine-dependent mice a direct effect of a low concentration of the residual drug?

ADDICTION BIOLOGY, Issue 4 2009
Vardit Rubovitch
ABSTRACT Withdrawal of opioid drugs leads to a cluster of unpleasant symptoms in dependent subjects. These symptoms are stimulatory in nature and oppose the acute, inhibitory effects of opiates. The conventional theory that explains the opioid withdrawal syndrome assumes that chronic usage of opioid drugs activates compensatory mechanisms whose stimulatory effects are revealed upon elimination of the inhibitory opioid drug from the body. Based on previous studies that show a dose-dependent dual activity of opiates, including pain perception, we present here an alternative explanation to the phenomenon of withdrawal-induced hyperalgesia. According to this explanation, the residual low concentration of the drug that remains after cessation of its administration elicits the stimulatory withdrawal hyperalgesia. The goal of the present study was to test this hypothesis. In the present study we rendered mice dependent on morphine by a daily administration of the drug. Cessation of morphine application elicited withdrawal hyperalgesia that was completely blocked by a high dose of the opiate antagonist naloxone (100 mg/kg). Similarly, naloxone (2 mg/kg)-induced withdrawal hyperalgesia was also blocked by 100 mg/kg of naloxone. The blockage of withdrawal hyperalgesia by naloxone suggested the involvement of opioid receptors in the phenomenon and indicated that withdrawal hyperalgesia is a direct effect of a residual, low concentration of morphine. Acute experiments that show morphine- and naloxone-induced hyperalgesia further verified our hypothesis. Our findings offer a novel, alternative approach to opiate detoxifications that may prevent withdrawal symptoms by a complete blockage of the opioid receptors using a high dose of the opioid antagonist. [source]

PRECLINICAL STUDY: Long-term haloperidol treatment (but not risperidone) enhances addiction-related behaviors in mice: role of dopamine D2 receptors

ADDICTION BIOLOGY, Issue 3 2009
Rita C. Carvalho
ABSTRACT The high prevalence of psychostimulant abuse observed in schizophrenic patients may be related to the development of mesolimbic dopaminergic supersensitivity (MDS) or nigrostriatal dopaminergic supersensitivity (NDS) in response to the chronic blockade of dopamine receptors produced by typical neuroleptic treatment. We compared the effects of withdrawal from long-term administration of the typical neuroleptic haloperidol (Hal) and/or the atypical agent risperidone (Ris) on MDS and NDS, behaviorally evaluated by amphetamine-induced locomotor stimulation (AILS) and apomorphine-induced stereotypy (AIS) in mice, respectively. We further evaluated the duration of MDS and investigated the specific role of dopamine D2 receptors in this phenomenon by administering the D2 agonist quinpirole (Quin) to mice withdrawn from long-term treatment with these neuroleptics. Withdrawal (48 hours) from long-term (20 days) Hal (0.5 mg/kg i.p.) (but not 0.5 mg/kg Ris i.p.) treatment potentiated both AILS and AIS. Ris co-administration abolished the potentiation of AILS and AIS observed in Hal-withdrawn mice. Ten days after withdrawal from long-term treatment with Hal (but not with Ris or Ris + Hal), a potentiation in AILS was still observed. Only Hal-withdrawn mice presented an attenuation of locomotor inhibition produced by Quin. Our data suggest that the atypical neuroleptic Ris has a pharmacological property that counteracts the compensatory MDS and NDS developed in response to the chronic blockade of dopamine receptors imposed by Ris itself or by typical neuroleptics such as Hal. They also indicate that MDS may be long lasting and suggest that an upregulation of dopamine D2 receptors in response to long-term treatment with the typical neuroleptic is involved in this phenomenon. [source]

Communication, Conflict, and Commitment: Insights on the Foundations of Relationship Success from a National Survey

FAMILY PROCESS, Issue 4 2002
Scott M. Stanley Ph.D.
The key relationship dynamics of communication, conflict, and commitment were investigated using data from a randomly sampled, nationwide phone survey of adults in married, engaged, and cohabiting relationships. Findings on communication and conflict generally replicated those of studies using more in depth or objective measurement strategies. Negative interaction between partners was negatively associated with numerous measures of relationship quality and positively correlated with divorce potential (thinking or talking about divorce). Withdrawal during conflict by either or both partners, thought quite common, was associated with more negativity and less positive connection in relationships. The most frequently reported issue that couples argue about in first marriages was money, and in re-marriages it was conflict about children. Overall, how couples argue was more related to divorce potential than was what they argue about, although couples who argue most about money tended to have higher levels of negative communication and conflict than other couples. Further, while the male divorce potential was more strongly linked to levels of negative interaction, the female was more strongly linked to lower positive connection in the relationship. Consistent with the commitment literature, higher reported commitment was associated with less alternative monitoring, less feeling trapped in the relationship, and greater relationship satisfaction. [source]

Potential pleiotropic effects of Mpdz on vulnerability to seizures

GENES, BRAIN AND BEHAVIOR, Issue 1 2004
C. Fehr
We previously mapped quantitative trait loci (QTL) responsible for approximately 26% of the genetic variance in acute alcohol and barbiturate (i.e., pentobarbital) withdrawal convulsion liability to a <,1 cM (1.8 Mb) interval of mouse chromosome 4. To date, Mpdz, which encodes the multiple PSD95/DLG/ZO-1 (PDZ) domain protein (MPDZ), is the only gene within the interval shown to have allelic variants that differ in coding sequence and/or expression, making it a strong candidate gene for the QTL. Previous work indicates that Mpdz haplotypes in standard mouse strains encode distinct protein variants (MPDZ1-3), and that MPDZ status is genetically correlated with severity of withdrawal from alcohol and pentobarbital. Here, we report that MPDZ status cosegregates with withdrawal convulsion severity in lines of mice selectively bred for phenotypic differences in severity of acute withdrawal from alcohol [i.e., High Alcohol Withdrawal (HAW) and Low Alcohol Withdrawal (LAW) lines] or pentobarbital [High Pentobarbital Withdrawal (HPW) and Low Pentobarbital Withdrawal (LPW) lines]. These analyses confirm that MPDZ status is associated with severity of alcohol and pentobarbital withdrawal convulsions. Using a panel of standard inbred strains of mice, we assessed the association between MPDZ status with seizures induced by nine chemiconvulsants. Our results show that MPDZ status is genetically correlated with seizure sensitivity to pentylenetetrazol, kainate and other chemiconvulsants. Our results provide evidence that Mpdz may have pleiotropic effects on multiple seizure phenotypes, including seizures associated with withdrawal from two classes of central nervous system (CNS) depressants and sensitivity to specific chemiconvulsants that affect glutaminergic and GABAergic neurotransmission. [source]

Alteration in Nature of Cluster Headache During Subcutaneous Administration of Sumatriptan

HEADACHE, Issue 1 2000
Rachel Hering-Hanit MD
Objectives., To document the relationship between the 5-HT receptor agonist sumatriptan and a change in the nature of cluster headache in four cases. To relate the findings to the literature on the use of sumatriptan in both cluster headache and migraine. Background., Studies of the efficacy and adverse effects of long-term treatment with sumatriptan in cluster headache are limited and report conflicting findings. Methods., Four cases are described. Results., All four patients developed a marked increase in the frequency of attacks 3 to 4 weeks after initiating treatment with the drug for the first time. Three patients also developed a change in headache character, and 2 experienced prolongation of the cluster headache period. Withdrawal of the drug reduced the frequency of headaches and eliminated the newly developed type of headache. Conclusions., Determination of the effects of long-term use of sumatriptan will result in more precise guidelines for the frequency and duration of treatment with this otherwise extremely beneficial drug. [source]

Withdrawal of Fall-Risk-Increasing Drugs in Older Persons: Effect on Tilt-Table Test Outcomes

JOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 5 2007
Nathalie Van Der Velde MD
OBJECTIVES: To determine whether outcomes of tilt-table tests improved after withdrawal of fall-risk-increasing drugs (FRIDs). DESIGN: Prospective cohort study. SETTING: Geriatric outpatient clinic. PARTICIPANTS: Two hundred eleven new, consecutive outpatients, recruited from April 2003 until December 2004. MEASUREMENTS: Tilt-table testing was performed on all participants at baseline. Subsequently, FRIDs were withdrawn in all fallers in whom it was safely possible. At a mean follow-up of 6.7 months, tilt-table testing was repeated in 137 participants. Tilt-table testing addressed carotid sinus hypersensitivity (CSH), orthostatic hypotension (OH), and vasovagal collapse (VVC). Odds ratios (ORs) of tilt-table-test normalization according to withdrawal (discontinuation or dose reduction) of FRIDs were calculated using multivariate logistic regression analysis. RESULTS: After adjustment for confounders, the reduction of abnormal test outcomes (ORs) according to overall FRID withdrawal was 0.34 (95% confidence interval (CI)=0.06,1.86) for CSH, 0.35 (95% CI=0.13,0.99) for OH, and 0.27 (95% CI=0.02,3.31) for VVC. For the subgroup of cardiovascular FRIDs, the adjusted OR was 0.13 (95% CI=0.03,0.59) for CSH, 0.44 (95% CI=0.18,1.0) for OH, and 0.21 (95% CI=0.03,1.51) for VVC. CONCLUSION: OH improved significantly after withdrawal of FRIDs. Subgroup analysis of cardiovascular FRID withdrawal showed a significant reduction in OH and CSH. These results imply that FRID withdrawal can cause substantial improvement in cardiovascular homeostasis. Derangement of cardiovascular homeostasis may be an important mechanism by which FRID use results in falls. [source]

Effect of Antipsychotic Withdrawal on Behavior and Sleep/Wake Activity in Nursing Home Residents with Dementia: A Randomized, Placebo-Controlled, Double-Blinded Study The Bergen District Nursing Home Study

JOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 10 2004
Sabine Ruths MD
Objectives: To explore the effect on sleep/wake activity and on behavioral and psychological symptoms of the withdrawal of antipsychotic medications from nursing home (NH) patients with dementia. Design: Randomized, placebo-controlled, double-blind trial. Setting: NHs in Bergen, Norway. Participants: Thirty patients (mean age 83.5) taking haloperidol, risperidone, or olanzapine for nonpsychotic symptoms. Intervention: Study participants were randomly assigned to withdrawal (intervention group) or continued treatment with antipsychotic medications (reference group) for 4 consecutive weeks. Measurements: Behavioral rating using the Neuropsychiatric Inventory Questionnaire (NPI-Q) and actigraphy. Results: After antipsychotic withdrawal, behavioral scores remained stable or improved in 11 of 15 patients, whereas four had worsening scores. Actigraphy revealed decreased sleep efficiency after drug discontinuation and increased 24-hour and night activity in both groups. Actigraphy records of nighttime and daytime activity indicated sleep problems and restlessness, in terms of the NPI-Q. One patient was restarted on antipsychotics. Conclusion: Antipsychotic drug withdrawal affected activity and sleep efficiency over the short term. Increases in total activity and impaired sleep quality after drug discontinuation should be monitored, because the long-term effect of these changes is not known. The NPI-Q and actigraphy are feasible tools that disclose relevant changes occurring during antipsychotic withdrawal in NH patients with dementia. Their use in clinical practice should be substantiated by larger studies. [source]

Effect of dexamethasone withdrawal on osteoblastic differentiation of bone marrow stromal cells

JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 1 2003
Ryan M. Porter
Abstract Dexamethasone is capable of directing osteoblastic differentiation of bone marrow stromal cells (BMSCs) in vitro, but its effects are not lineage-specific, and sustained exposure has been shown to down-regulate collagen synthesis and induce maturation of an adipocyte subpopulation within BMSC cultures. Such side effects might be reduced if dexamethasone is applied in a regimented manner, but the discrete steps in osteoblastic maturation that are stimulated by dexamethasone are not known. To examine this, dexamethasone was added to medium to initiate differentiation of rat BMSCs cultures and then removed after a varying number of days. Cell layers were analyzed for cell number, rate of collagen synthesis, expression of osteocalcin (OC), bone sialoprotein (BSP) and lipoprotein lipase (LpL), and matrix mineralization. Withdrawal of dexamethasone at 3 and 10 days was found to enhance cell number relative to continuous exposure, but did not affect to decrease collagen synthesis slightly. Late markers of osteoblastic differentiation, BSP expression and matrix mineralization, were also sensitive to dexamethasone and increased systematically with exposure while LpL systematically decreased. These results indicate that dexamethasone acts at both early and late stages to direct proliferative osteoprogenitor cells toward terminal maturation. J. Cell. Biochem. 90: 13,22, 2003. © 2003 Wiley-Liss, Inc. [source]

Solifenacin-induced small bowel pseudo-obstruction

JOURNAL OF HOSPITAL MEDICINE, Issue 2 2008
Naveen Pemmaraju MD
Abstract An 89-year-old woman was admitted to Johns Hopkins Hospital with a small bowel obstruction and symptoms of urinary retention. She had been started on solfenacin for bladder overactivity 10 days prior to her presentation. Withdrawal of the solfenacin resulted in a full recovery, which has persisted for greater than 6 months without surgical intervention. This is the first reported case report of small bowel pseudo-obstruction due to solifenacin. Journal of Hospital Medicine 2008;3:176,178. © 2008 Society of Hospital Medicine. [source]

Organizational Justice and Individuals' Withdrawal: Unlocking the Influence of Emotional Exhaustion

JOURNAL OF MANAGEMENT STUDIES, Issue 3 2010
Michael S. Cole
abstract This study examined the relationships between organizational justice and withdrawal outcomes and whether emotional exhaustion was a mediator of these linkages. Data were obtained from 869 military personnel and civil servants; using structural equation modelling techniques, we examined an integrative model that combines justice and stress research. Our findings suggest that individuals' justice perceptions are related to their psychological health. As predicted, emotional exhaustion mediated the linkages between distributive and interpersonal (but not procedural and informational) justice and individuals' withdrawal reactions. Results showed that distributive and interpersonal justice negatively related to emotional exhaustion and emotional exhaustion negatively related to organizational commitment which, in turn, negatively influenced turnover intentions. These findings were observed even when controlling for the presence of contingent-reward behaviours provided by supervisors and individuals' psychological empowerment. [source]

Work Relationships in Telephone Call Centres: Understanding Emotional Exhaustion and Employee Withdrawal

JOURNAL OF MANAGEMENT STUDIES, Issue 4 2002
Stephen Deery
This paper examines the nature of employment and the conditions of work in five telephone call centres in the telecommunications industry in Australia. Call centre work typically requires high levels of sustained interpersonal interaction with customers which can lead to burnout and employee withdrawal. Customer service staff can also become targets of customer hostility and abuse. In addition, this form of work tends to involve extensive employee monitoring and surveillance with little job discretion or variety of tasks. The paper draws upon survey data from 480 telephone service operators to identify the factors that are associated with emotional exhaustion and the frequency of absence amongst the employees. A modelling of the data using LISREL VIII revealed that a number of job and work-setting variables affected the level of emotional exhaustion of employees. These included interactions with the customer, a high workload and a lack of variety of work tasks. Moreover, higher rates of absence were associated with emotional exhaustion. [source]

Robust stimulation of TrkB induces delayed increases in BDNF and Arc mRNA expressions in cultured rat cortical neurons via distinct mechanisms

JOURNAL OF NEUROCHEMISTRY, Issue 2 2007
Makoto Yasuda
Abstract In cultures of rat cortical neurons, we found that stimulation of tyrosine receptor kinase B (TrkB) with brain-derived neurotrophic factor (BDNF) induced a biphasic expression of BDNF exon IV,IX mRNA, which became obvious 1,3 h (primary induction) and 24,72 h (delayed induction) after the stimulation, and characterized the delayed induction in relation to the mRNA expression of activity-regulated cytoskeleton-associated protein (Arc). Withdrawal of BDNF from the medium after stimulation for 3 h allowed the delayed induction, which was caused at the transcriptional level and dependent upon the initial contact between exogenously added BDNF and TrkB, the effect of which was time- and dose-dependent. The primary induction was controlled by the extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) whereas the secondary induction by the calcium (Ca2+) signaling pathway. The enhanced Arc or Zif268 mRNA expression was controlled by activation of the ERK/MAPK pathway, both of which were repressed by blocking the binding of endogenously synthesized BDNF to TrkB. Thus, robust stimulation of TrkB autonomously induces delayed BDNF mRNA expression in an activity-dependent manner in rat cortical neurons, resulting in the stimulation of Arc mRNA expression through endogenously synthesized BDNF, the process being orchestrated by the Ca2+ and ERK/MAPK signaling pathways. [source]

Withdrawal of neonatal mechanical ventilation against the parents' wishes

JOURNAL OF PAEDIATRICS AND CHILD HEALTH, Issue 5 2006
David Isaacs
Abstract: Neonatologists and parents usually agree when intensive treatment should be stopped. We describe the management of two babies where there was disagreement between the parents and hospital staff, and discuss the medical, legal and ethical implications of the two cases. [source]

QT Interval Dispersion and Cardiac Sympathovagal Balance Shift in Rats With Acute Ethanol Withdrawal

ALCOHOLISM, Issue 2 2010
Seiko Shirafuji
Background:, Dysregulation of autonomic nervous system function and impaired homogeneity of myocardial repolarization are 2 important mechanisms for the genesis of ventricular arrhythmias in nonalcoholic subjects. Our previous study suggested that acute ethanol withdrawal promoted the shift of cardiac sympathovagal balance toward sympathetic predominance and reduced the vagal tone, which were related to a higher incidence of ventricular arrhythmia and related death. However, the homogeneity of myocardial repolarization and its relation with the cardiac sympathovagal balance are unknown, especially in alcoholic subjects. The aim of the present study was to clarify these points. Methods:, Male Wistar rats were treated with a continuous ethanol liquid diet for 49 days, and then subjected to 1-day withdrawal and 1-day withdrawal with 7-day carvedilol (can block the sympathetic nervous system completely via ,1, ,2, and , adrenergic receptors) pretreatment. The cardiac sympathovagal balance and homogeneity of myocardial repolarization were evaluated based on the heart rate variability (HRV) and QT interval dispersion (QTd: dynamic changes in QT interval duration). Results:, The increase in QTd was observed only in rats at 1-day withdrawal, but not in nonalcoholic, continuous ethanol intake, and 1-day withdrawal with 7-day carvedilol pretreatment rats. At 1-day withdrawal, the low-frequency power/high-frequency power (LF/HF) ratio in HRV was elevated and correlated with the QTd. The increased QTd and elevated LF/HF ratio were normalized by the 7-day carvedilol pretreatment in rats at 1-day ethanol withdrawal. Conclusions:, In rats with an abrupt termination of the chronic continuous ethanol intake, the homogeneity of myocardial repolarization impaired and correlated with the cardiac sympathovagal balance. Carvedilol pretreatment is associated with a reduction in both the QTd and LF/HF ratio, raising the possibility that the cardiac sympathovagal balance shift may be responsible for the impaired homogeneity of myocardial repolarization, and that ,-blocker pretreatment may decrease the mortality risk during alcoholic withdrawal. [source]

Neuropeptide S Receptor Gene Expression in Alcohol Withdrawal and Protracted Abstinence in Postdependent Rats

ALCOHOLISM, Issue 1 2010
Barbara Ruggeri
Background:, Alcoholism is a chronic disease characterized by frequent intoxications followed by withdrawal episodes and relapse to alcohol use. Neuroplastic changes associated with these intoxication and withdrawal cycles are thought to play a key role in disease progression. Recently, it has been shown that neuropeptide S (NPS), a newly deorphanized neuropeptide receptor system, facilitates relapse to alcohol seeking in laboratory animals. Given that a history of ethanol intoxication may increase vulnerability to alcohol addiction, we sought to determine whether NPS receptor (NPSR) gene expression is altered during withdrawal. Methods:, Rats were subjected to 1 week of intoxication by oral alcohol administration. NPSR gene expression was analyzed by in situ hybridization in rats 12 hours and 7 days after the last alcohol administration. To investigate the functional significance of NPSR system adaptation following protracted withdrawal 7 days after intoxication, we tested the anxiolytic-like properties of NPS in nondependent and postdependent rats using the shock probe defensive burying test (DB). Results:, At both time points, increased NPSR gene expression was observed in several brain areas, including the endopiriform nucleus, the motor cortex, and the medial amygdaloid nucleus. Moderate increases in gene expression were also found in the lateral hypothalamus, paraventricular nucleus, basolateral and central amygdala. Differences from control animals were more pronounced after 7 days of abstinence. The upregulation of the NPSR system at this time point was confirmed by functional data indicating that intracerebroventricular (ICV) NPS administration (0.0, 0.3, and 0.1 nmol/rat) elicits more pronounced anxiolytic effects in postdependent animals than in controls subjected to the electric shock probe DB test. Conclusions:, Neuropeptide S receptor mRNA expression is increased in different brain areas of postdependent rats; as shown in the DB test, this expression change is functionally relevant. [source]

Selected Line Difference in the Effects of Ethanol Dependence and Withdrawal on Allopregnanolone Levels and 5,-Reductase Enzyme Activity and Expression

ALCOHOLISM, Issue 12 2009
Michelle A. Tanchuck
Background:, Allopregnanolone (ALLO) is a progesterone derivative that rapidly potentiates ,-aminobutyric acidA (GABAA) receptor-mediated inhibition and modulates symptoms of ethanol withdrawal. Because clinical and preclinical data indicate that ALLO levels are inversely related to symptoms of withdrawal, the present studies determined whether ethanol dependence and withdrawal differentially altered plasma and cortical ALLO levels in mice selectively bred for differences in ethanol withdrawal severity and determined whether the alterations in ALLO levels corresponded to a concomitant change in activity and expression of the biosynthetic enzyme 5,-reductase. Methods:, Male Withdrawal Seizure-Prone (WSP) and -Resistant (WSR) mice were exposed to 72 hours ethanol vapor or air and euthanized at select times following removal from the inhalation chambers. Blood was collected for analysis of ALLO and corticosterone levels by radioimmunoassay. Dissected amygdala, hippocampus, midbrain, and cortex as well as adrenals were examined for 5,-reductase enzyme activity and expression levels. Results:, Plasma ALLO was decreased significantly only in WSP mice, and this corresponded to a decrease in adrenal 5,-reductase expression. Cortical ALLO was decreased up to 54% in WSP mice and up to 46% in WSR mice, with a similar decrease in cortical 5,-reductase activity during withdrawal in the lines. While cortical gene expression was significantly decreased during withdrawal in WSP mice, there was a 4-fold increase in expression in the WSR line during withdrawal. Hippocampal 5,-reductase activity and gene expression was decreased only in dependent WSP mice. Conclusions:, These results suggest that there are line and brain regional differences in the regulation of the neurosteroid biosynthetic enzyme 5,-reductase during ethanol dependence and withdrawal. In conjunction with the finding that WSP mice exhibit reduced sensitivity to ALLO during withdrawal, the present results are consistent with the hypothesis that genetic differences in ethanol withdrawal severity are due, in part, to modulatory effects of GABAergic neurosteroids such as ALLO. [source]

Differential Effects of Chronic Ethanol Consumption and Withdrawal on Homer/Glutamate Receptor Expression in Subregions of the Accumbens and Amygdala of P Rats

ALCOHOLISM, Issue 11 2009
Ilona Obara
Background:, Homer proteins are constituents of scaffolding complexes that regulate the trafficking and function of central Group1 metabotropic glutamate receptors (mGluRs) and N -methyl- d -aspartate (NMDA) receptors. Research supports the involvement of these proteins in ethanol-induced neuroplasticity in mouse. In this study, we examined the effects of short versus long-term withdrawal from chronic ethanol consumption on Homer and glutamate receptor protein expression within striatal and amygdala subregions of selectively bred, alcohol-preferring P rats. Methods:, For 6 months, male P rats had concurrent access to 15% and 30% ethanol solutions under intermittent (IA: 4 d/wk) or continuous (CA: 7 d/wk) access conditions in their home cage. Rats were killed 24 hours (short withdrawal: SW) or 4 weeks (long withdrawal: LW) after termination of ethanol access, subregions of interest were micropunched and tissue processed for detection of Group1 mGluRs, NR2 subunits of the NMDA receptor and Homer protein expression. Results:, Within the nucleus accumbens (NAC), limited changes in NR2a and NR2b expression were detected in the shell (NACsh), whereas substantial changes were observed for Homer2a/b, mGluRs as well as NR2a and NR2b subunits in the core (NACc). Within the amygdala, no changes were detected in the basolateral subregion, whereas substantial changes, many paralleling those observed in the NACc, were detected in the central nucleus (CeA) subregion. In addition, most of the changes observed in the CeA, but not NACc, were present in both SW and LW rats. Conclusions:, Overall, these subregion specific, ethanol-induced increases in mGluR/Homer2/NR2 expression within the NAC and amygdala suggest changes in glutamatergic plasticity had taken place. This may be a result of learning and subsequent memory formation of ethanol's rewarding effects in these brain structures, which may, in part, mediate the chronic relapsing nature of alcohol abuse. [source]