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Drug Withdrawal (drug + withdrawal)
Selected AbstractsAntiepileptic Drug Withdrawal after Successful Surgery for Intractable Temporal Lobe EpilepsyEPILEPSIA, Issue 2 2005Young 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] Does antipsychotic withdrawal provoke psychosis?ACTA PSYCHIATRICA SCANDINAVICA, Issue 1 2006Review of the literature on rapid onset psychosis (supersensitivity psychosis), withdrawal-related relapse Objective:, To examine the evidence that discontinuation of long-term antipsychotic medication, including clozapine, may provoke a psychotic episode. Method:, Databases were searched and citations scrutinised. Results:, Evidence for a rapid onset psychosis (supersensitivity psychosis) following clozapine withdrawal was found and weaker evidence that this might occur with some other antipsychotic drugs. Some cases were reported in people without a psychiatric history. It appears that the psychosis may be a feature of drug withdrawal rather than the re-emergence of an underlying illness, at least in some patients. Meta-analyses of withdrawal studies have suggested that antipsychotic discontinuation may also increase the risk of relapse over and above the risk because of the underlying disorder, but not all individual studies show this effect. Mechanisms may relate to brain adaptations to long-term drug use but data are sparse. Conclusion:, These effects require further urgent research. Interventions to reduce morbidity after drug withdrawal need to be developed. [source] REVIEW: Nicotine self-medication of cognitive-attentional processingADDICTION BIOLOGY, Issue 1 2009David E. Evans ABSTRACT This article selectively reviews research concerning nicotine's effects on cognition, including the neurobiological mechanism for these effects, task and experimental features that may be important for elucidating these effects, and why these effects may have amplified motivational significance among smokers with cognitive deficit. Nicotine has effects on various cognitive processes, though most studies in humans have focused on the amelioration of cognitive deficits experienced during drug withdrawal. The direct cognitive-enhancing effect of nicotine remains a controversial topic. The relationship between attentional and non-attentional cognitive effects of nicotine is discussed in the context of cognitive self-medication. Further research should include theory-driven examination of cognitive effects of nicotine, and develop targeted smoking cessation programs based on an improved understanding of the role of cognitive self-medication in high-risk individuals. [source] Previous experience of withdrawal from chronic diazepam ameliorates the aversiveness of precipitated withdrawal and reduces withdrawal-induced c-fos expression in nucleus accumbensEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2000Sarah J. Dunworth Abstract Flumazenil (20 mg/kg, i.p.)-precipitated withdrawal from chronic treatment with diazepam (DZP, 15 mg/kg, s.c. in sesame oil for 21 days) resulted in a decreased seizure threshold to the convulsant, pentylenetetrazole (PTZ), infused into the tail vein; withdrawal from 21-day chronic diazepam treatment, interspersed with two periods of drug withdrawal, resulted in a greater decrease in convulsant threshold. A separate experiment showed that consumption of a sucrose solution immediately prior to precipitated withdrawal resulted in a decreased subsequent consumption of the sucrose solution; no such evidence of a conditioned taste aversion (CTA) was seen in mice given prior experience of withdrawal. Thus, prior experience of withdrawal enhanced the effects of a subsequent precipitated withdrawal in increasing seizure sensitivity, but weakened the ability of this withdrawal to serve as an aversive unconditioned stimulus (US). The weakening of the aversive properties of precipitated withdrawal may reflect habituation to the withdrawal stimulus, and was accompanied by a loss of the ability of withdrawal to induce c-fos expression in the shell of the nucleus accumbens, an area sensitive to both novel, and stressful, as well as rewarding stimuli. [source] Comprehensive Inpatient Treatment of Refractory Chronic Daily HeadacheHEADACHE, Issue 4 2009Alvin E. Lake III PhD Objective., (1) To assess outcome at discharge for a consecutive series of admissions to a comprehensive, multidisciplinary inpatient headache unit; (2) To identify outcome predictors. Background., An evidence-based assessment (2004) concluded that many refractory headache patients appear to benefit from inpatient treatment, underscoring the need for more research, including outcome predictors. Methods., The authors completed a retrospective chart review of 283 consecutive admissions over 6 months. The inpatient program (mean length of stay = 13.0 days) included intravenous and oral medication protocols, drug withdrawal when indicated, cognitive-behavior therapy, and other services when needed, including anesthesiological intervention. Patient-reported pain levels and consensus of medical staff determined outcome status. Results., The 267 completers (94%) included 212 women and 55 men (mean age = 40.3 years, range = 13-74) from 43 states and Canada. The modal diagnosis was intractable, chronic daily headache (85%), predominantly migraine. Most (59%) had medication overuse headache (MOH), involving opioids (48%), triptans (16%), or butalbital-containing analgesics (10%). Psychiatric diagnoses included stress-related headache (82%), mood disorders (70%), anxiety disorders (49%), and personality disorders (PD, 26%). More patients with a PD (62%) had opioid-related MOH than those with no PD (38%), P < .005. Of the completers, 78% had moderate to significant pain reduction, with comparable improvement in mood, function, and behavior. Clinical factors predicting moderate-significant headache improvement were limited to MOH (84% vs 69%, P < .007) and presence of a PD (68% vs 81%, P < .03). Conclusions., Most patients (78%) improved following aggressive, comprehensive inpatient treatment. Maintenance of improvement is likely to depend on multiple post-discharge factors, including continuity of care, compliance, and home or work environment. [source] Prophylaxis of Hemicrania Continua: Two New Cases Effectively Treated With TopiramateHEADACHE, Issue 3 2007Filippo Brighina MD Hemicrania continua (HC) is an uncommon and under-recognized primary headache disorder characterized by a strictly unilateral continuous headache of moderate intensity with possible exacerbations and associated with ipsilateral autonomic features. HC has generally a prompt and enduring response to indomethacin although 25% to 50% of treated patients develop gastrointestinal side effects. These cases pose a difficult management challenge as no other drug is consistently effective in HC. Recently 2 HC patients responsive to topiramate treatment have been reported. Here we describe 2 more patients effectively treated with topiramate. Neither reported any side effects and one had persisting response for 6 months after drug withdrawal. [source] Response of refractory colitis to intravenous or oral tacrolimus (FK506)INFLAMMATORY BOWEL DISEASES, Issue 5 2002Dr. Klaus Fellermann Abstract Intravenous cyclosporine has proven to be an alternative to emergency colectomy in steroid-refractory ulcerative colitis, whereas the experience with FK506 is limited. In this report we compare intravenous to oral FK506 treatment in 38 patients with refractory ulcerative (n = 33) or indeterminate (n = 5) colitis. FK506 was started intravenously in the first group (n = 18) at a dose of 0.01 to 0.02 mg/kg up to 14 days, followed by 0.1 to 0.2 mg/kg orally, or was started orally at this dose in a second group (n = 20). Additional azathioprine/6-mercaptopurine was given and steroids were tapered in responding patients, followed by a dose reduction of FK506. Clinical disease activity and laboratory parameters were assessed to evaluate efficacy and safety. Primary objectives were the induction of remission (Truelove index of mild) and colectomy-free survival. Treatment lasted for a mean of 7.6 months, and the mean observation period was 16.2 months. Eighteen of 38 patients improved within 14 days, and a complete remission was achieved in 13 patients after 1 month. A colectomy within 1 month was performed in 3 of 38 patients. The overall colectomy rate was 34%. One-half of the patients with a minimum follow-up of 2 years required a colectomy. Intravenous and per oral administration were equally safe and effective. The most frequent adverse events included tremor, hyperglycemia, hypertension, and infection, but none were severe. Renal impairment was rare and subsided upon drug withdrawal. In conclusion, FK506 is effective in the treatment of refractory colitis with per oral dosing being equivalent to intravenous administration. [source] Vorinostat increases carboplatin and paclitaxel activity in non-small cell lung cancer cellsINTERNATIONAL JOURNAL OF CANCER, Issue 3 2010Taofeek K. Owonikoko Abstract We observed a 53% response rate in non-small cell lung cancer (NSCLC) patients treated with vorinostat plus paclitaxel/carboplatin in a Phase I trial. Studies were undertaken to investigate the mechanism (s) underlying this activity. Growth inhibition was assessed in NSCLC cells by MTT assay after 72 hr of continuous drug exposure. Vorinostat (1 ,M) inhibited growth by: 17% ± 7% in A549, 28% ± 6% in 128-88T, 39% ± 8% in Calu1 and 41% ± 7% in 201T cells. Vorinostat addition to carboplatin or paclitaxel led to significantly greater growth inhibition than chemotherapy alone in all 4 cell lines. Vorinostat (1 ,M) synergistically increased the growth inhibitory effects of carboplatin/paclitaxel in 128-88T cells. When colony formation was measured after drug withdrawal, vorinostat significantly increased the effects of carboplatin but not paclitaxel. The % colony formation was control 100%; 1 ,M vorinostat, 83% ± 10%; 5 ,M carboplatin, 41% ± 11%; carboplatin/vorinostat, 8% ± 4%; 2 nM paclitaxel, 53% ± 11%; paclitaxel/vorinostat, 46% ± 21%. In A549 and 128-88T, vorinostat potentiated carboplatin induction of gamma-H2AX (a DNA damage marker) and increased ,-tubulin acetylation (a marker for stabilized mictrotubules). In A549, combination of vorinostat with paclitaxel resulted in a synergistic increase in ,-tubulin acetylation, which reversed upon drug washout. We conclude that vorinostat interacts favorably with carboplatin and paclitaxel in NSCLC cells, which may explain the provocative response observed in our clinical trial. This likely involves a vorinostat-mediated irreversible increase in DNA damage in the case of carboplatin and a reversible increase in microtubule stability in the case of paclitaxel. [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 StudyJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 10 2004Sabine 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] Chronic Naltrexone Treatment and Ethanol Responsivity in Outbred RatsALCOHOLISM, Issue 2 2010Katherine G. Hill Background:, Acute naltrexone treatment in rats produces significant alterations in ethanol palatability (increase in the aversiveness of the solution) and ethanol consumption during tests of restricted access (decrease in consumption). The effects of chronic naltrexone exposure, accomplished by implantation of osmotic mini-pumps, were examined in the present study. Methods:, Rats were surgically implanted with intraoral fistulae for taste reactivity testing. The animals were given 2 bottles (distilled water and 10% ethanol, v/v) for 3, 2-week phases: Pre-Drug, Drug, and Post-Drug. After the Pre-Drug phase, rats were assigned to groups (counterbalanced based on ethanol intake) and implanted with a mini-pump containing saline, 7.5 mg/kg/d naltrexone, or 15 mg/kg/d naltrexone. The pumps were removed 2 weeks later. During each 2-week phase, taste reactivity tests with 10% ethanol were conducted at 1, 7, and 14 days (a total of 9 reactivity tests). Results:, The 7.5 mg/kg/d dose produced only minor effects on 10% ethanol reactivity and consumption during the Drug phase. The 15 mg/kg/d naltrexone dose generally shifted taste reactivity responding to 10% ethanol in a negative direction and produced a transient decrease in ethanol consumption. The 15 mg/kg/d group significantly increased ethanol consumption beyond the level of consumption by the Saline group when the pumps were removed, although the increase was delayed 48 hours. By the end of the Post-Drug period, this naltrexone group returned to control levels of ethanol consumption. Conclusions:, Chronic naltrexone treatment at 15 mg/kg/d significantly decreased the palatability of a 10% ethanol solution, an effect seen even after drug withdrawal. Naltrexone had a minor effect on ethanol consumption during treatment but did decrease overall levels of fluid consumption. The significant increase in ethanol consumption postdrug by the high-dose naltrexone group, presumably due to receptor up-regulation during treatment, is important and understanding this effect and developing means of overcoming it within a clinical practice would be useful goals. [source] Consequences of treatment withdrawal in type 1 autoimmune hepatitisLIVER INTERNATIONAL, Issue 4 2007Aldo J. Montano-Loza Abstract Background and Aims: Drug-related side effects are considered the major consequences of relapse and re-treatment in patients with autoimmune hepatitis. Our goals were to determine whether relapse is associated with disease progression and whether treatment end points can be refined. Methods: The outcomes of 132 patients with definite type 1 autoimmune hepatitis who had been treated comparably until remission were assessed retrospectively after drug withdrawal. Results: Patients who had relapsed repeatedly after initial treatment withdrawal developed cirrhosis more commonly than patients who sustained remission (18/48 vs 1/22, P=0.004), and those who relapsed once (18/48 vs 2/21, P=0.02). Hepatic death or the need for liver transplantation was also more frequent in the patients who had multiple relapses than those who sustained remission (13/64 vs 0/30, P=0.008) and those who relapsed once (13/64 vs 1/38, P=0.02). Patients who sustained their remission had a higher frequency of normal laboratory indices at drug withdrawal than patients who relapsed (88% vs 46%, P=0.003). Adverse outcomes after relapse did not distinguish patients until after 5 years of observation. Conclusions: Multiple relapses are associated with a poorer prognosis than sustained remission or single relapse episodes. Initial treatment to resolution of laboratory abnormalities may afford the greatest opportunity to prevent relapse. [source] EAACI/GA2LEN guideline: aspirin provocation tests for diagnosis of aspirin hypersensitivityALLERGY, Issue 10 2007E. Ni, ankowska-Mogilnicka Abstract:, Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most common causes of adverse drug reactions. Majority of them are of the hypersensitivity type. The two frequent clinical presentations of aspirin hypersensitivity are: aspirin-induced bronchial asthma/rhinosinusitis (AIA/R) and aspirin-induced urticaria/angioedema (AIU). The decisive diagnosis is based on provocation tests with aspirin, as the in vitro test does not hold diagnostic value as yet. Detailed protocols of oral, bronchial and nasal aspirin provocation tests are presented. Indications, contraindications for the tests, the rules of drug withdrawal and equipment are reviewed. Patient supervision and interpretations of the tests are proposed. [source] A systematic review of NSAIDs withdrawn from the market due to hepatotoxicity: lessons learned from the bromfenac experience,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 4 2006Lawrence Goldkind MD Abstract Drug-induced hepatotoxicity is the leading cause of acute liver failure (ALF) in the US and the most common adverse event causing drug non-approval and drug withdrawal by the U.S. Food and Drug Administration (FDA). Three different nonsteroidal anti-inflammatory drugs (NSAIDs) have been withdrawn in the UK and/or the US due to hepatotoxicity (bromfenac, ibufenac, and benoxaprofen). A systematic review of clinical trials data for these drugs was performed in an effort to identify possible early signals that could have predicted post-marketing serious hepatoxicity. There were very limited published data on benoxaprofen and none on ibufenac or bromfenac. The publicly accessible archives of the FDA provided information on bromfenac. Flu-like symptoms associated with hepatic enzyme elevation and a case of possible drug-related hepatocellular jaundice may in retrospect have been signals for serious hepatotoxicity in the database of 1195 subjects reviewed by the FDA. Following approval, rates of acute liver failure for bromfenac were estimated to be in the range of 1:10,000. In addition, the safety databases of several drugs also accessed through FDA archives have been reviewed (simvastatin, tacrine, troglitazone, and ximelagatran). These data suggest that while ALT elevations alone do not reliably signal serious hepatotoxicity, elevated transaminases in association with symptomatic hepatitis or jaundice may be predictors of an increased risk of ALF. At present, however, pre-approval databases are generally not large enough to rule out low rates of serious hepatotoxicity. Therefore, it remains critical that clinicians report such cases to the FDA through the MEDWATCH system and that active post-marketing monitoring studies be used to identify potential rare cases of hepatotoxicity. Copyright © 2006 John Wiley & Sons, Ltd. [source] Dendritic Cell Subset Ratio in Peripheral Blood Correlates with Successful Withdrawal of Immunosuppression in Liver Transplant PatientsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 6 2003George V. Mazariegos Human dendritic cell (DC) subsets appear to play distinct roles in the induction and regulation of immune responses. While monocytoid DC (DC1) induce T-helper (Th) 1-type responses, plasmacytoid DC (DC2) have been reported to selectively induce Th2 responses. In blood, their precursors (p) can be identified as HLA-DR+ lineage, cells that are further characterized as CD11c+ CD123,/lo (IL-3R,,/lo) (pDC1) or as CD11c, CD123hi (pDC2) by rare event, flow cytometric analysis. We compared the incidences of pDC1 and pDC2 in peripheral blood mononuclear cell populations isolated from normal healthy controls and from 3 groups of clinically stable liver transplant patients. Group A had been successfully withdrawn from immunosuppression, whereas group B were undergoing prospective drug weaning and on minimal anti-rejection therapy. In group C, drug withdrawal had either failed or never been attempted and patients were on maintenance immunosuppression. Assessment of DC subsets and the pDC2 : pDC1 ratio showed good intra-and interassay reproducibility. Compared with patients in group C, those in groups A and B demonstrated a significantly higher relative incidence of pDC2 and a lower incidence of pDC1 , similar to those values observed in normal healthy controls. Moreover, the pDC2 : pDC1 ratio was significantly higher in patients undergoing (successful) weaning and in those off immunosuppression compared with patients on maintenance immunosuppression. [source] Withdrawal of antiepileptic drugs after neocortical epilepsy surgeryANNALS OF NEUROLOGY, Issue 2 2010Kyung-Il Park MD Objective This study investigated the prevalence of successful antiepileptic drug withdrawal and identified predictors of seizure recurrence after antiepileptic drug reduction following resectional operation for intractable neocortical epilepsy. Methods We retrospectively assessed 223 patients (100 with neocortical temporal lobe epilepsy, 69 with frontal lobe epilepsy, 23 with parietal lobe epilepsy, 25 with occipital lobe epilepsy, and 6 with multifocal epilepsy) who underwent surgery. The mean period of observation was 84.4 months (range, 24,152 months) after surgery and 72.6 months (range, 12,138 months) after initial reduction. Clinical characteristics, magnetic resonance imaging, and surgical parameters were evaluated for their potential to predict recurrence associated with antiepileptic drug withdrawal. Results Antiepileptic drug reduction was attempted in 147 patients (65.9%), 78 (53.1%) of whom had seizure recurrence after initial reduction. Discontinuation was achieved in 73 patients (32.7%), and 59 (80.8%) of these remained seizure free until final assessment. Multivariate analysis revealed that early drug tapering, normal magnetic resonance imaging results, seizure before reduction, and longer epilepsy duration were associated with recurrence. Finally, 27.4% of patients were seizure free without drugs, and 26.9% were seizure free with drugs. Compared with preoperative status, the number of antiepileptic drugs needed decreased in 50.7% of patients, did not change in 19.3%, and increased in 30.0% after surgery. Interpretation The complete-cure rate of intractable neocortical epilepsy by resectional surgery was 27.4%. When patients undertake early tapering, and have normal magnetic resonance imaging results, seizure before reduction, and longer disease duration, further withdrawal should be done cautiously because of the high risk of relapse. ANN NEUROL 2010;67:230,238 [source] Direct comparison of treatment responses, remission rates, and drug adherence in patients with rheumatoid arthritis treated with adalimumab, etanercept, or infliximab: Results from eight years of surveillance of clinical practice in the nationwide Danish DANBIO registryARTHRITIS & RHEUMATISM, Issue 1 2010Merete Lund Hetland Objective To compare tumor necrosis factor , inhibitors directly regarding the rates of treatment response, remission, and the drug survival rate in patients with rheumatoid arthritis (RA), and to identify clinical prognostic factors for response. Methods The nationwide DANBIO registry collects data on rheumatology patients receiving routine care. For the present study, we included patients from DANBIO who had RA (n = 2,326) in whom the first biologic treatment was initiated (29% received adalimumab, 22% received etanercept, and 49% received infliximab). Baseline predictors of treatment response were identified. The odds ratios (ORs) for clinical responses and remission and hazard ratios (HRs) for drug withdrawal were calculated, corrected for age, disease duration, the Disease Activity Score in 28 joints (DAS28), seropositivity, concomitant methotrexate and prednisolone, number of previous disease-modifying drugs, center, and functional status (Health Assessment Questionnaire score). Results Seventy percent improvement according to the American College of Rheumatology criteria (an ACR70 response) was achieved in 19% of patients after 6 months. Older age, concomitant prednisolone treatment, and low functional status at baseline were negative predictors. The ORs (95% confidence intervals [95% CIs]) for an ACR70 response were 2.05 (95% CI 1.52,2.76) for adalimumab versus infliximab, 1.78 (95% CI 1.28,2.50) for etanercept versus infliximab, and 1.15 (95% CI 0.82,1.60) for adalimumab versus etanercept. Similar predictors and ORs were observed for a good response according to the European League Against Rheumatism criteria, DAS28 remission, and Clinical Disease Activity Index remission. At 48 months, the HRs for drug withdrawal were 1.98 for infliximab versus etanercept (95% 1.63,2.40), 1.35 for infliximab versus adalimumab (95% CI 1.15,1.58), and 1.47 for adalimumab versus etanercept (95% CI 1.20,1.80). Conclusion Older age, low functional status, and concomitant prednisolone treatment were negative predictors of a clinical response and remission. Infliximab had the lowest rates of treatment response, disease remission, and drug adherence, adalimumab had the highest rates of treatment response and disease remission, and etanercept had the longest drug survival rates. These findings were consistent after correction for confounders and sensitivity analyses and across outcome measures and followup times. [source] Investigation into the effects of cidofovir on an in vitro model of recurrent respiratory papillomatosisCLINICAL OTOLARYNGOLOGY, Issue 3 2006A.J. Donne Problem. Recurrent respiratory papillomatosis (RRP) has no cure, and cidofovir is currently the most contemporary adjuvant treatment. Cidofovir has reported activity against Human Papilloma Virus type 16, but no laboratory studies have yet been performed on HPV type 6 which is the main cause of RRP. This work describes the generation of a novel HPV 6 related cell line and its use to evaluate the effects of Cidofovir. Method. HPV6b E6 cDNA was stably introduced into HPV negative C33A cervical carcinoma cells to produce the C33AT6E6 cell line. Two different doses of Cidofovir were applied to parent C33A, C33AT6E6 and C33AT16E6 (type 16 cell line) with appropriate controls. Growth and FACS cell cycle analysis were performed after 3 and 6 days of continuous exposure followed by 2 and 3 days post-drug withdrawal. Result.PCR analysis confirmed HPV6 E6 expression in C33AT6E6 cells. High dose cidofovir was toxic at 3 and 6 days exposure in all cells tested. Low dose exposure was toxic for C33AT16E6 cells at 3 days whereas C33A and C33AT6E6 only showed minimal toxicity at 6 days. C33A and C33AT6E6 cells also showed earlier recovery following drug withdrawal. Conclusion.Cidofovir showed varying degrees of non-specific toxicity against all three cell lines tested. However, HPV16 E6 expressing cells were more sensitive than either parent or HPV6 E6 expressing cells indicating that cidofovir has no selective advantage for the RRP related HPV6 E6 expressing cell line. [source] Hyperphagia, weight gain and neonatal drug withdrawalACTA PAEDIATRICA, Issue 9 2002R Shephard Hyperphagia, a classical feature of neonatal drug withdrawal, has been reported not to lead to excessive weight gain, but this is contrary to our clinical experience. The aim of this study was to determine whether infants with neonatal drug withdrawal suffered excessive weight gain because of hyperphagia and, if so, to determine the risk factors. The study population comprised 48 infants consecutively admitted to the neonatal intensive care unit, 11 of whom gained weight by more than 20 g kg -1 d -1 for at least 10 d (excessive weight gain). All 11 infants were hyperphagic (>200 ml/kg) for at least part of the excessive weight gain period. During the perinatal period, the 11 infants had a greater fluid intake (p > 0.01) but similar weight gain to gestational-age-matched, neonatal drug-withdrawal infants who did not suffer any excessive weight gain. Compared to the rest of the cohort, the infants with excessive weight gain were more likely to require treatment with morphine/chlorpromzaine (p > 0.05) and had a higher maximum withdrawal score (p > 0.01). Conclusion: Hyperphagia can lead to excessive weight gain in infants with neonatal drug withdrawal. Our results suggest that hyperphagia occurs in those who require treatment for severe withdrawal. [source] | |||||||||||||