Time Of Drug Withdrawal Research Articles

Analysis of the Efficacy and Safety of PEGylated Interferon-α2b Treatment in Inactive HepatitisB Surface Antigen Carriers.

IntroductionHepatitis B virus (HBV) infection is associated with the onset of several major liver diseases. Inactive hepatitis B surface antigen (HBsAg) carriers (IHCs) may be successfully treated with PEGylated interferon-α2b (PEG-IFNα2b)-based antiviral therapy; however, studies on this treatment have been insufficient. In this study, we evaluated the efficacy and safety of PEG-IFNα2b treatment in IHCs.MethodsNineteen IHCs were treated with subcutaneous PEG-IFNα2b (180 μg/week) for 48 weeks (treatment group). Patients were followed up for 24 weeks after treatment discontinuation. Twenty untreated control patients were observed for 72 weeks (control group). HBsAg clearance (HBsAg < 0.05 IU/mL), HBsAg seroconversion, and alanine aminotransferase levels were monitored.ResultsOf the 19 patients treated with PEG-IFNα2b, 16 showed HBsAg loss (84.2%), and 13 showed HBsAg seroconversion (68.4%) at 72 weeks. All patients in the treatment group exhibited virological response (serum HBV DNA level < 10 IU/mL) at the time of drug withdrawal. In the control group, no patients experienced HBsAg loss during the observational period. There were no serious adverse events during treatment, and the therapy was well tolerated.ConclusionsShort PEG-IFNα2b therapy in IHCs produced a high functional cure rate and good safety profile, suggesting that PEG-IFNα2b treatment may be the best choice for clinical cure of some IHCs.

Microstructural features of the cerebral cortex: Implications for predicting epilepsy relapse after drug withdrawal

A considerable portion of patients with well-controlled seizures and visually normal brain structures experience seizure recurrence after anti-seizure medication is withdrawn. Microstructural abnormalities of the cortex may play an essential role in epilepsy relapse. Patients with idiopathic/cryptogenic epilepsy were registered. At the follow-up endpoint, 18 patients with relapse (PR+ group), 20 patients without relapse (PR− group), and 30 healthy controls were included. High-resolution T1-weighted images were obtained at the time of drug withdrawal. Microstructural features including cortical thickness, surface area, cortical volume and mean curvature in 68 cortical areas were calculated. A general linear model was applied to investigate intergroup differences, and then post hoc analysis was performed. Additionally, factor analysis was conducted to extract components from imaging measures showing a difference between PR− and PR+ groups, and independent associations between components and epilepsy relapse were assessed using a logistic regression model. Cortical thickness of the left paracentral lobule, left temporal pole and right superior frontal gyrus; surface area of the bilateral lingual gyrus and bilateral pericalcarine cortex; and cortical volume of the bilateral pericalcarine cortex had significant intergroup differences (false discovery rate correction, P < 0.05). All measures, except for cortical thickness of the left temporal pole, showed differences between PR− and PR+ groups. Two dominant components were extracted from these measures, and both were independently associated with epilepsy relapse. In conclusion, epilepsy patients with relapse presented distinct microstructural features of cortex at the time of drug withdrawal, which may serve as a potential biomarker for predicting seizure recurrence.

The correlation between interleukin-21 and the recurrence of chronic hepatitis B after entecavir discontinuation

Objective To study the correlation between interleukin (IL)-21 and the recurrence of chronic hepatitis B (CHB) in hepatitis B e antigen (HBeAg)-positive patients after discontinuation of entecavir (ETV). Methods A total of 112 HBeAg-positive CHB patients treated with ETV were enrolled. Serum levels of IL-21 at week 0, 12, 24 and 52 after ETV discontinuation were detected. The Cox regression model was used to analyze the correlation between IL-21 and the recurrence after ETV discontinuation. The receiver operating characteristic (ROC) curve was applied to determine the predictive value of IL-21 for CHB recurrence after ETV discontinuation. The expression differences of IL-21 were compared between sustained viral response (SVR) group and viral relapse (VR) group. The t test and Chi-square test were used for statistical analysis. Results The serum levels of IL-21 in SVR group at week 0, 12, 24 and 52 after ETV withdrawal were (60.0±10.8), (60.2±14.7), (60.6±19.5) and (61.2±15.4) ng/L, respectively, which were all significantly higher than those in VR group (47.5±10.7), (47.3±12.9), (46.9±12.2) and (46.4±12.8) ng/L, respectively (t=6.153, 4.926, 4.382 and 5.515, respectively, all P<0.01). The area under curve (AUC) was 0.811 (95%CI: 0.728~0.893, P<0.01) and the best cut-off value of serum IL-21 level was 49.8 ng/L. The recurrence rates of patients with serum IL-21 level ≥49.8 ng/L and <49.8 ng/L at time of ETV withdrawal was 25.4% (16/63) and 77.6% (38/49), respectively. The difference was statistically significant (χ2=30.027, P<0.01). The serum IL-21 level at the time of drug withdrawal (P=0.005), serum hepatitis B surface antigen (HBsAg) level at the time of HBeAg seroconversion (P=0.008) and age (P=0.016) were factors associated with CHB recurrence after ETV withdrawal by multivariate Cox model analysis. The serum levels of ALT, HBV DNA, HBeAg and HBsAg in SVR group were significantly lower than those of VR group at week 12, 24 and 52 after ETV withdrawal (t=-5.968, -7.691, -8.093; -3.047, -9.477, -28.900; -2.872, -10.424, -18.330; -4.633, -4.030 and -5.032, respectively; all P<0.01). Serum level of IL-21 was negatively correlated with HBsAg in SVR group after ETV withdrawal (r=-0.241, P<0.01), while positively correlated with HBsAg in VR group (r=0.286, P<0.01). Conclusions The serum IL-21 level at the time of drug withdrawal is associated with the recurrence after ETV discontinuation. IL-2l may play an important role as an immunomodulatory factor in maintaining virological responses in HBeAg-positive CHB patients after ETV withdrawal. Key words: Cytokines; Hepatitis B, chronic; Recurrence; Entecavir; Withdrawal

Establishment of a prognostic model for clinical relapse after drug withdrawal in chronic hepatitis B patients with hepatitis B e antigen seroconversion

Objective To investigate the prognostic factors for clinical relapse in chronic hepatitis B (CHB) patients with hepatitis B e antigen (HBeAg) seroconversion after drug withdrawal and to establish a prognostic model. Methods Totally 201 CHB patients with HBeAg seroconversion after the antiviral therapy were enrolled. The epidemiological variables including age, gender and family history of hepatitis B were collected. Liver function and hepatitis B virus (HBV) DNA level one week before initiation of antiviral therapy, hepatitis B surface antigen (HBsAg) level at the time of drug withdrawal and the duration of antiviral therapy after HBeAg seroconversion were analyzed. The clinical relapse after 48 weeks of drug withdrawal was followed up. The patients were divided into relapse group and non-relapse group according to clinical variables at 48 weeks after drug withdrawal. The counting data were analyzed by chi-square test and the measurement data were analyzed by t test. The Logistic regression model was used to determine the prognostic factors for clinical relapse. The receiver operating charactenstic (ROC) curve was constructed to assess the performance of the prediction model. Results The clinical relapse rate was 16.42% (33/201) after 48 weeks of drug withdrawal. By multivariate analysis, age, the duration of antiviral therapy after HBeAg seroconversion and HBsAg level at the time of drug withdrawal were independent predictors (χ2=14.546, t=3.202, t=3.286, respectively; all P<0.05). The regression model Logit (P)=1.220×age-0.040×the duration of antiviral therapy after HBeAg seroconversion + 0.004×HBsAg level at the time of drug withdrawal -5.426. The sensitivity and specificity with the cut-off value of -0.860 were 73.10% and 90.40%, respectively. Conclusions Age, the duration of antiviral therapy after HBeAg seroconversion and HBsAg level at the time of drug withdrawal are independent predictors for clinical relapse 48 weeks after drug withdrawal in CHB patients with HBeAg seroconversion after antiviral therapy. Key words: HBeAg seroconversion; Clinical relapse; Prognostic model; Logistic regression analysis

Mean Platelet Volume in Graves' disease: A Sign of Hypermetabolism Rather than Autoimmunity?

Objective:To evaluate the impact of mean platelet volume (MPV) on predicting disease course among patients with Graves’ disease (GD).Methods:This retrospective study was performed between 2013-2016 at the Outpatient Endocrinology Clinic of Baskent University Faculty of Medicine, Adana hospital on 65 patients with GD. Among participants, 30 cases experienced thyrotoxicosis again during the first six months after discontinuing anti-thyroid drug (ATD) sessions that had been carried out for at least 12 months prior to stopping (Relapse group). We also observed 35 patients who exhibited normal thyroid functions within six months following ATD withdrawal (Remission group). MPV levels and thyroid function tests were recorded and total duration of ATD therapy was calculated for all participants.Results:The mean MPV level that was measured at the time of drug withdrawal did not differ between groups, being 8.0±1.2 fL in the Relapse group vs. 8.0±1.0 fL in the Remission group (p=0.81). However, we found that the relapse MPV was higher than the withdrawal MPV in the Relapse group (9.2±1.3 fL) than it was in the Remission group (8.0±1.2 fL, p=0.00).Conclusions:Higher relapse MPV in Relapse group but similar MPV levels in both groups at ATD withdrawal may be attributed to hypermetabolism or hyperthyroidism rather than autoimmunity of GD.Abbreviations:BMI: Body mass indexGD: Graves’ diseaseMPV: Mean platelet volumeTSH: Thyroid-stimulating hormoneTRAbs: Thyrotropin receptor antibodiesATD: Anti-thyroid drugfT4: Free thyroxinefT3: Free triiodothyronineCBC: Complete blood countPTC: Papillary thyroid carcinoma

Usefulness of Measuring Thyroid Stimulating Antibody at the Time of Antithyroid Drug Withdrawal for Predicting Relapse of Graves Disease.

BackgroundHyperthyroidism relapse in Graves disease after antithyroid drug (ATD) withdrawal is common; however, measuring the thyrotropin receptor antibody (TRAb) at ATD withdrawal in order to predict outcomes is controversial. This study compared measurement of thyroid stimulatory antibody (TSAb) and thyrotropin-binding inhibitory immunoglobulin (TBII) at ATD withdrawal to predict relapse.MethodsThis retrospective study enrolled patients with Graves disease who were treated with ATDs and whose serum thyroid-stimulating hormone levels were normal after receiving low-dose ATDs. ATD therapy was stopped irrespective of TRAb positivity after an additional 6 months of receiving the minimum dose of ATD therapy. Patients were followed using thyroid function tests and TSAb (TSAb group; n=35) or TBII (TBII group; n=39) every 3 to 6 months for 2 years after ATD withdrawal.ResultsTwenty-eight patients (38%) relapsed for a median follow-up of 21 months, and there were no differences in baseline clinical characteristics between groups. In the TSAb group, relapse was more common in patients with positive TSAb at ATD withdrawal (67%) than patients with negative TSAb (17%; P=0.007). Relapse-free survival was shorter in TSAb-positive patients. In the TBII group, there were no differences in the relapse rate and relapse-free survivals according to TBII positivity. For predicting Graves disease relapse, the sensitivity and specificity of TSAb were 63% and 83%, respectively, whereas those of TBII were 28% and 65%.ConclusionTSAb at ATD withdrawal can predict the relapse of Graves hyperthyroidism, but TBII cannot. Measuring TSAb at ATD withdrawal can assist with clinical decisions making for patients with Graves disease.

Valuable predictive features of relapse of Graves’ disease after antithyroid drug treatment

PurposeAntithyroid drug treatment (ATDT) effectively achieves euthyroidism in patients with Graves’ disease (GD). However, apparently successful treatment may be followed by relapse. We investigated the outcome of ATDT in Chinese patients with GD to identify predictive features of relapse. MethodsIn total, 133 patients with mild to moderate goiter were included in this analysis. All patients received methimazole for 12 to 40months and were subsequently followed up for at least 1year. Lasting remission was defined as the presence of clinical and laboratory features of euthyroidism for≥1year after stopping methimazole. ResultsMost patients (118 of 133, 88.7%) remained in remission after the follow-up period; 15 patients (11.3%) developed relapse. A history of GD, larger goiter at the time of drug withdrawal, a positive thyroid-stimulating antibody titer and restauration of low thyroid-stimulating hormone levels during the maintenance period were related to a subsequent risk of relapse according to stepwise logistic regression analysis results. However, other clinical and biological features (age, sex, initial goiter, ophthalmopathy, thyroxine and triiodothyronine levels and thyroglobulin antibody and thyroid microsomal antibody titers) did not reach statistical significance. ConclusionRegular, individualized ATDT achieved an 88.7% remission rate in Chinese patients with GD. The features associated with probable relapse were a history of GD, larger goiter at the time of drug withdrawal, a positive thyroid-stimulating antibody titer at the time of drug withdrawal and redevelopment of low thyroid-stimulating hormone levels during the maintenance period.

Relapse is almost universal after withdrawal of immunosuppressive medication in patients with autoimmune hepatitis in remission

Current treatment strategies in autoimmune hepatitis (AIH) include long-term treatment with corticosteroids and/or azathioprine. Here we determined the risk of relapse after drug withdrawal in patients in long-term remission and factors associated with such a relapse. A total of 131 patients (out of a cohort including 844 patients) from 7 academic and 14 regional centres in the Netherlands were identified in whom treatment was tapered after at least 2 years of clinical and biochemical remission. Relapse was defined as alanine-aminotransferase levels (ALT) three times above the upper limit of normal and loss of remission as a rising ALT necessitating the reinstitution of drug treatment. During follow-up, 61 (47%) patients relapsed and 56 (42%) had a loss of remission. In these 117 patients, 60 patients had fully discontinued medication whereas 57 patients were still on a withdrawal scheme. One year after drug withdrawal, 59% of the patients required retreatment, increasing to 73% and 81% after 2 and 3 years, respectively. Previous combination therapy of corticosteroids and azathioprine, a concomitant autoimmune disease and younger age at time of drug withdrawal were associated with an increased risk of relapse. Subsequent attempts for discontinuation after initial failure in 32 patients inevitably resulted in a new relapse. This retrospective analysis indicates that loss of remission or relapse occurs in virtually all patients with AIH in long-term remission when immunosuppressive therapy is discontinued. These findings indicate a reluctant attitude towards discontinuation of immunosuppressive treatment in AIH patients.

Determination of risk factors associated with seizure relapse after antiepileptic drug withdrawal

Abstract There is no consensus regarding the time of antiepileptic drug withdrawal and the relevant risk factors for seizure relapse. In this study, we aimed to determine the seizure relapse rates and the associated risk factors for seizure relapse in childhood epilepsy. Two-hundred sixty-six epileptic patients who discontinued the antiepileptic drug therapy after a seizure-free period of at least two years, were enrolled into the study. The data of the patients regarding sex, febrile convulsion history, family history, age at onset, type of epilepsy, total number of seizures and antiepileptic drugs, seizures during treatment, mental status, first and last electroencephalography, brain imaging findings, etiological factors and seizure relapse in the first two years after antiepileptic drug withdrawal were obtained from the patients’ files. Univariate logistic regression analysis was performed for each variable. The variables which were found to be statistically significant in univariate analysis, were included in multivariate logistic regression analysis. The overall seizure relapse rate after antiepileptic drug withdrawal was 19.2%. There were no significant differences for seizure relapse rate after antiepileptic drug withdrawal between patient groups with respect to sex, family history, type of epilepsy, febrile convulsion history, seizures before treatment, first electroencephalography findings, brain imaging findings and etiology. However, there were statistically significant differences for seizure relapse rate among patient groups concerning age at onset of epilepsy, new seizure during treatment, the total number of antiepileptic drugs, mental status, and last electroencephalography findings. We imply that the clinical status of the patients should be considered before the cessation of drug therapy rather than the etiological factors or laboratory findings.

Related factors in predicting relapse of Graves' disease after treatment with antithyroid drugs

Objective To explore the value of thyroid-stimulating antibody(TSAb) and degree of goiter in predicting the outcome of Graves'disease after antithyroid drug treatment. Methods Seventy-one patients with Graves'disease were given antithyroid drugs for (2. 8±1. 4)years and then followed up for(22±6.0)months.Finally,age,gender,thyroid function,TSAb and goiter size at the time of drug withdrawal were compared between the relapsed and relieved groups. TSAb was measured in all patients by using HEK-hTSHR cells. Results Eleven of 71 patients relapsed during the follow-up after drug withdrawal. The relapse rate (42. 9% ,6/14)in patients with positive TSAb was significantly higher than that (8.8%, 5/57) in patient with negative TSAb (X2 = 9.97, P<0.01). The relapse rates in patients with normal size thyroid, Ⅰ degree goiter,Ⅱ degree goiter were 6.25%, 12.2%,35.7% respectively. TSAb activity, positive rate and goiter size of the relapsed patients at the time of drug withdrawal were significantly higher than those of relieved patients (P<0.05 or P<0. 01). Conclusion TSAb activity and goiter size at the time of drug withdrawal are two effective prognostic markers of relapse in Graves' disease treated with antithyroid drugs. Key words: Graves' disease; Thyroid-stimulating antibody; HEK-hTSHR ; Relapse

Effects of haloperidol on rat behavior and density of dopaminergic D2-like receptors.

The present work shows the effects of a typical neuroleptic drug (haloperidol, HAL) on rat behavior (catalepsy and locomotor activity) and dopaminergic D2-like receptor densities in the hippocampus and striatum. Male Wistar rats (2-3 months old) were treated daily for 30 days with HAL (0.2 or 1mg/kg, intraperitoneally (i.p.)). At the end of treatment and 1h or 1, 3, 7 and 15 days after drug withdrawal, animals were subjected to behavioral tests and sacrificed afterwards for binding assays. The results showed that behavioral effects with both doses were significant only 1h and 1 day after withdrawal, and similar to controls at the third day. An up-regulation of D2 receptors was observed in the striatum (28% increase) but not in the hippocampus after 24h HAL (1mg/kg) withdrawal. However, an up-regulation was seen in both areas (1mg/kg) 3 days after drug withdrawal (58 and 42% increases in the hippocampus and striatum, respectively), and continued after 7 days of withdrawal only in the striatum (43 and 49% for the doses of 0.2 and 1mg/kg, respectively), suggesting the influence of dose, age, and time of drug withdrawal on these parameters. The up-regulation disappeared after 15 days of haloperidol withdrawal. Increases (72 and 140%) in constant dissociation values (K(d)) values were also observed 7 days after withdrawal. Results show differences on a time-basis between behavioral alterations and dopaminergic D2 receptors up-regulation.

Thyrotropin-releasing hormone-induced GH release after cocaine withdrawal in cocaine addicts

During cocaine addiction the hypothalamus–pituitary axis is widely affected and a blunted response of thyroid stimulating hormone (TSH) to thyroid releasing hormone (TRH) consistent with a hyperthyroid state has been observed. Since the thyroid status can affect the release of growth hormone (GH) the authors evaluated TSH and GH responses to TRH in cocaine addicts at the time of drug withdrawal and 30 days after. Twenty-six male cocaine addicts and 11 healthy male control subjects agreed to participate in the study. TRH and placebo tests were performed at random at 5 day intervals at the time of drug withdrawal and after 30 days. In drug addicts, at the time of the first test basal plasma levels of freeT3, freeT4 and TSH were normal, but the TSH response to TRH was impaired. After 30 days of cocaine abstinence basal freeT4 plasma levels were significantly lower, and TSH levels and the TSH response to TRH were higher than in the first test. At the first examination, basal GH concentrations were similar in cocaine addicts and in control subjects and GH did not respond to TRH. After 30 days of abstinence, basal GH plasma levels were unmodified, but the TRH became stimulatory of GH release in cocaine-deprived, but not in control subjects. In conclusion, in cocaine addicts, drug withdrawal is associated with a condition of subclinical hypothyroidism that makes the GH-releasing machinery sensitive to TRH.

Behavior and significance of autoantibodies in type 1 autoimmune hepatitis

Background/Aim: Smooth muscle antibodies and antinuclear antibodies characterize type 1 autoimmune hepatitis. Our aim was to correlate the appearance and disappearance of these autoantibodies with clinical and histological events. Methods: One hundred and seven patients were evaluated successively over 128±9 months. Autoantibodies were determined by indirect immunofluorescence during routine follow-up and at key clinical events. Results: Eighty-one patients (76%) lost one or both of the autoantibodies, and disappearance was associated with improved laboratory and histological features. Autoantibody status, however, was not highly predictive of laboratory (69%) or histological activity (72%). Patients who relapsed were seronegative at the time of drug withdrawal as commonly as patients who sustained remission (29% versus 25%). Only 27 patients (25%) lost their autoantibodies long term. Patients who eventually entered a sustained remission lost their autoantibodies more commonly than those who required retreatment (76% versus 43%, p=0.03). Disappearance of the autoantibodies, however, preceded sustained remission in only 38%. Serum titers at presentation did not distinguish patients with more severe disease or different treatment outcomes. Conclusions: Smooth muscle antibodies and antinuclear antibodies commonly disappear and reappear. Their loss is associated with improved laboratory tests and biopsy findings, but disappearance does not predict treatment outcome. Autoantibody titer at presentation and autoantibody behavior during therapy are not accurate indices of disease severity or prognosis.

Early Withdrawal From Repeated Cocaine Administration Upregulates Muscarinic and Dopaminergic D2-Like Receptors in Rat Neostriatum

The present results show an increase in locomotor activity 24 h following repeated cocaine administration only with the higher dose (10 mg/kg, IP, daily for 1 week) compared to controls (administered with saline). Binding assays were done and the ligands used were [3H]N-methylscopolamine ([3H]-NMS), [3H]-SCH 23390, and [3H]-spiroperidol to determine muscarinic (M1- and M2-like), D1 and D2 receptors, respectively. Scatchard analyses revealed alterations in Bmax not only for muscarinic, but also for D2-like receptors that were significantly increased. On the other hand, no alterations were detected on D1-like receptors densities and dissociation constant values. However, the Kd value was significantly increased for D2 receptors. The changes in muscarinic receptors were observed predominantly on M2-like, which presented an increase of 84% with the 10 mg/kg, IP, dose only. On D2-like receptors, increases of 63 and 54% were demonstrated with the doses of 5 and 10 mg/kg, IP. The preferential effects of cocaine on muscarinic and D2-like receptors were also demonstrated in vitro where decreases in [3H]-NMS and [3H]-spiroperidol binding were observed. The results indicate that the effects of cocaine on muscarinic and dopaminergic postsynaptic receptors are functions of dose, duration of treatment, and time of drug withdrawal.

A Practical Guide to Discontinuing Antiepileptic Drugs

Up to 70% of those individuals who develop epilepsy achieve remission from seizures for a period of 2 or more years. On average about 30% of those who are withdrawn from antiepileptic drug treatment will experience further seizures within 2 years. Patients with childhood onset epilepsy that is not symptomatic and that is associated with a normal electroencephalogram at the time of drug withdrawal are at the lowest risk of seizure recurrence. In contrast, juvenile myoclonic epilepsy is a contraindication to drug withdrawal. The risk of seizure recurrence appears to decrease with increasing length of remission (up to 5 years) before consideration of drug withdrawal.

Prospective study of the need for long-term antisecretory therapy in patients with Zollinger-Ellison syndrome following successful curative gastrinoma resection.

A long-term cure is now possible in more than 30% of selected patients with Zollinger-Ellison syndrome who undergo gastrinoma resection. The need, however, for continued gastric acid antisecretory therapy in these patients remains controversial. The current study was designed to determine whether post-operative antisecretory therapy is needed in patients who have undergone successful gastrinoma resection and, if so, to attempt to define criteria with which to identify patients who require therapy. Twenty-eight consecutive patients who had previously undergone curative gastrinoma resection were prospectively studied. When antisecretory therapy was discontinued, 43% (12/28) of these patients developed gastro-oesophageal reflux, diarrhoea, acid-peptic symptoms or endoscopic evidence of acid-peptic disease within 2 weeks and were deemed to have failed a trial of antisecretory drug withdrawal. The remaining 57% (16/28) of patients who successfully discontinued antisecretory therapy were followed for a mean time of 31 months after withdrawal of therapy. Analysis of acid output studies pre-operatively, as well as at the time of drug withdrawal, demonstrated that patients who were unable to discontinue antisecretory therapy exhibited higher pre-operative maximal acid output values and higher basal acid output values at the time of attempted drug withdrawal than patients who were able to discontinue therapy. Despite these findings, there was significant overlap in acid output values between groups so that it was not possible to define specific acid output criteria for successful drug withdrawal. Pre-operative clinical characteristics, such as the presence or absence of gastro-esophageal reflux or acid-peptic disease, or post-operative laboratory values, such as the fasting serum gastrin level, did not correlate with the ability to discontinue antisecretory therapy. We conclude that following successful curative gastrinoma resection, 40% of patients still require antisecretory therapy and that both symptom evaluation as well as upper endoscopy should be used to guide attempted drug withdrawal. Although patients who are not able to discontinue therapy have significantly higher acid output measurements than those who are able to discontinue therapy, neither acid output criteria nor any other laboratory or clinical characteristics are able to predict the need for continued antisecretory therapy in these patients.

Drug Use and Misuse in Chronic Pain Patients

Narcotic and tranquillizer abuse is extremely common in chronic pain patients and continued drug use is an insurmountable barrier to adequate pain rehabilitation. Proper drug use assessment and withdrawal techniques are essential, and some patients should be hospitalized for safe withdrawal. Proper education of the nursing staff is essential for adequate detoxification management. Alternative techniques for pain control provide an invaluable support during the very difficult time of drug withdrawal for the patient.

VALUE OF THYROID-STIMULATING-ANTIBODY DETERMINATIONS IN PREDICTING SHORT-TERM THYROTOXIC RELAPSE IN GRAVES' DISEASE

Thirty consecutive patients with hyper-thyroid Graves' disease received a 6-month course of antithyroid drugs. Sixteen patients relapsed within 6 months of the withdrawal of antithyroid therapy. All patients with high levels of thyroid-stimulating antibodies (TSAb) at the time of drug withdrawal relapsed within 2 months of discontinuing the antithyroid treatment while all patients with low or undetectable TSAb activity at the time of drug withdrawal remained in remission. It was not possible to predict the disease course in patients who had intermediate levels of TSAb when antithyroid therapy was stopped.

Clinical, toxicological, and pathological aspects of arsanilic acid poisoning in swine.

In Trial I, toxicosis was induced in 27 pigs by feeding 1000 ppM arsanilic acid in the ration. The clinical syndrome was first characterized by transient diarrhea and incoordination, with posterior paresis and quadriplegia later. Detectable histopathological changes were confined to the optic tracts, optic nerves, and peripheral nerves. Major lesions noted were necrosis of myelin-supporting cells and degeneration of myelin sheaths and axons. Maximum mean arsenic levels were present in liver, kidney, skeletal muscle, rib, and blood on or before day 13 of the experiment. Maximum mean arsenic levels in the nervous system were not attained until days 19 and 21. In Trial II, six pigs were fed 1000 ppM arsanilic acid in the ration for 19 days. Three days after the removal of dietary arsanilic acid, skeletal muscle, kidney, liver, and blood, respectively, retained 31, 34, 32, and 13 mean % of the tissue arsenic present at the time of drug withdrawal. Nervous tissue retained 100, 93, 57 mean % arsenic 3, 6, and 11 days post-withdrawal, respectively. In Trial III, six pigs were fed 1000 ppM arsanilic acid in the ration until they developed severe posterior paresis or quadriplegia. Four pigs had no clinical improvement and twomore » pigs developed a more severe paralysis after withdrawal of the drug. 12 references, 10 figures, 5 tables.« less